N-Boc-propargylamine

Pale Yellow Low Melting Solid

Di-tert-butyl dicarbonate (17.5 g, 80.0 mmol, 1.0 equiv) was added dropwise at 0 °C to a soln of prop-2-yn-1-amine (5.49 mL, 80.0 mmol, 1.0 equiv) in CH(7a): 5.5 g of propargylamine (100 mmol) was dissolved in 50 mL of ethyl acetate, Boc anhydride (32 g, 147 mmol) was added under ice-water bath, The reaction was allowed to warm to room temperature overnight, The organic phase was washed with 1percent hydrochloric acid solution, Saturated sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate and spun dry to give product 13 as a yellow solid (15.3 g, 99 mmol, 1 99percent).test-Butyl prop-2-ynylcarbamate (46). To a solution of propargylamine (803 mg, 14.6 mmol) in CH2C12 (15 mL) at 0 °C was added a solution of di-tert-butyl dicarbonate (2.67 g, 15.3 mmol) in CH2C12 (20 mL) via dropping funnel over 25 min, the ice bath was removed and the resultant solution was stirred at ambient temperature for 30 min. The solvent was removed in vacuo and the crude material was chromatographed on silica gel (EtOAc/Hex, 10/90, Rf= 0.28) to afford the title compound 46 (2.23 g, 98percent yield) as a white solid: mp = 39-40 °C ; 1H NMR (CDC13) 8 4.79 (s, 1H), 3.90 (br s, 2H), 2.20 (m, 1H), 1.43 (s, 9H); LRMS (ESI) m/z calcd for CsHl3NNa02 [M + Na] + 178, found 178.Step A: tert-Butyl prop-2-ynylcarbamate: A solution of propargylamine (5.00 gProp-2-ynyl-carbamic acid tert-butyl ester 2:BocHNDi-tert-butyl dicarbonate (9.0g, 40.0mmol) was added to a solution ofpropargylamine (2.0g, 36.0mmol) and triethylamine (7.6ml_, 54.5mmol) in dichloromethane (20ml_) at rt. After overnight stirring, the reaction was washed with saturated solution of NHTo a stirred solution of propargyl amine (2.0 g, 36.3 mmol) in THF (30 mL) was added di-tert-butyl dicarbonate (8.78 g, 40.2 mmol, 1.1 equiv) at rt. The solution was stirred at the same temperature for 4h, and then concentrated in vacuo. The resulting residue was dissolved in EtOAc (100 mL), washed with water (3×20 mL) and brine (20 mL) and then dried over anhydrous NaPreparation of Compound 29Step B: Preparation of tert-butyl prop-2-ynylcarbamate: A solution of propargylamine (5.00 g, 90.8 mmol) and BoCStep B: Preparation of tert-butyl prop-2-ynylcarbamate: A solution of propargylamine (5.00 g, 90.8 mmol) and BoCTo a solution of compound 154 (500 mg, 9.00 mmol) in CHDi-tert-butyl-dicarbonate (10 g, 47 mmol, 1 equiv.) was dissolved in CH2Cl2 (0.2 M) and cooledd own to 0 C. 3-Amino-1-propyne (2.6 g, 47 mmol, 1 equiv.) was added at 0 C over a period of 30 min. Then, the mixture was allowed to warm to room temperature and stirred for 2 hours. When the reaction was completed by TLC, the solvent was evaporated and n-Pentane was added. The solution was left on standing in the refrigerator for 12 h. The precipitate was collected by filtration to afford 6 g of the N-Boc-propargylamine (82percent) as a white solid.To a stirred solution of propargylamine (0.83 mL, 12.9mmol, 1 eq.) in dry DCM (13 mL) under nitrogen, was added dropwise a solution of di-tert-butyldicarbonate (2.81 g, 12.9 mmol, 1 eq.) in dry DCM (7 mL) and the reaction was stirred for 2 h.The organic layer was washed with an aqueous solution of HCl (1 N), then with a saturatedaqueous solution of NaHCO3. The aqueous layer was extracted with DCM, then the combinedorganic layers were dried over MgSO4, filtered and concentrated under vacuum. The cruderesidue was purified by flash column chromatography on silica gel (cyclohexane/EtOAc: 80/20)to afford tert-butyl prop-2-yn-1-ylcarbamate (1.6 g 10.4 mmol, 80percent) as a white solid. Thiscompound has been previously reported.S1A solution of 1.28 ml (6.00 mmol, 1.1 eq.) of Boc2O in 15 ml of dry CH2Cl2 was addeddropwise to a solution of 0.348 ml (5.45 mmol, 1.0 eq.) of propargyl amine in 15 ml of dryCH2Cl2 at 0°C. The reaction mixture was stirred at r.t. for 1 h. After TLC showed completeconsumption of starting material, solvent was removed under reduced pressure. The crudeproduct was purified by flash column chromatography (cHex/EtOAc 20:1 – 10:1). Theproduct was obtained as an off-white solid (yield: 0.667 g, 4.303 mmol, 79 percent).Di-tert-butyl-dicarbonate (21.8 mg, 100.0 mmol) was dissolved in THF (25 mL) and the solution cooled to 0° C. and treated dropwise with a solution of propargylamine (Aldrich, 5.0 g, 90.0 mmol) keeping the temperature below 15° C. The mixture was stirred at rt for 1.5 h then concentrated under vacuum. The residue was dissolved in hexanes and filtered through a column of silica gel using 0-100percent CHtert -butyl prop-2-yn-l-ylcarbamate (7) [0153] Into a reactor was added propagylamine (10.0kg, 182mol) and MTBE (154L). A B0C2O solution was prepared by dissolving B0C2O (41.3kg, 190 mol) in MTBE (61L) and transferred over a minimum of 60min to the propargyamine solution while maintaining a temperature between 23 and 28 °C. The reaction mixture was stirred for at least lh until >98.0percent conversion was obtained by GC analysis. A solution of sodium bisulfate (5.6kg of NaHSC>4 n 44L water) was added over a minimum of 15min while maintaining the temperature between 20 and 25 °C and stirred for 20min. The phases were separated and washed as before with a solution of sodium bisulfate (5.6kg of NaHSC>4 To a solution of 2-PROPYN-1-AMINE (2 g, 36.4 mmol, 1 equiv) in CH2CI2 (20 mi) were added NEt3 (5.3 MI, 38.18 MMOL, 1.05 equiv) and bis (1, 1-dimethylethyl) dicarbonate (8.32 g, 38.18 mmol, 1.05 equiv). The resulting mixture was stirred at room temperature for 3 h then poured in a 2N aqueous HCI solution. The two layers were separated and the organic phase was washed with a saturated aqueous NAHC03 solution then dried over MGS04 and concentrated in VACUO TO give 1, 1-dimethylethyl 2-propyn-1-ylcarbamate (D317) (4.05 g, 72percent) as a colourless crystal.To a solution OF 2-PROPYN-1-AMINE (2 g, 36.36 mmol, 1 equiv) in CH2CI2 (20 ML) at room temperature were added NEt3 (5.3 ml, 38.18 mmol, 1.05 equiv) and bis (1, 1- dimethylethyl) dicarbonate (8.32 g, 38.18 mmol, 1.05 equiv) and the resulting mixture was stirred at room temperature for 3 h then washed with a 2N aqueous HCI solution and a saturated NAHC03 aqueous solution, dried over MGS04 and concentrated in vacuo to give 1, 1-DIMETHYLETHYL 2-PROPYN-1-YLCARBAMATE (D38) (4.05 g, 72percent) as colourless needles which were used in the next step without further purification.(0049) To a solution of prop-2-yn-1-amine (5.0 g, 90.9 mmol) and Et3N (18.4 g, 181.8 mmol) in DCM (100 mL) was added (Boc)2O (23.8 g, 109.1 mmol) dropwise while cooling the reaction mixture with an ice bath. The resulting mixture was removed from the ice bath once the addition was completed, and was then stirred at room temperature for 16 h. When the reaction was complete, the mixture was diluted with DCM (200 mL), washed with brine (100 mL_3), and the organic layer was then dried over Na2SO4 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE:EtOAc=100:1÷10:1) to give 1672-1 (10 g, 71percent) as a colorless oil. MS 178.3 [M+23]+, 100.3 [M_56]+.EXAMPLE 516A Propargyl amine (25.18 g, 0.448 mol), triethylamine (55.52 g, 0.549 mol) and dichloromethane 400 ml were added to a four-necked flask, and while cooling the reaction solution in a water bath (20 ° C.) Di-tert-butyl carbonate (118.15 g, 0.541 mol) was added dropwise over 30 minutes. After completion of the dropwise addition, after stirring for 2 hours, 300 ml of saturated brine and 200 ml of dichloromethane were added to the reaction solution and extracted. The obtained organic layer was dried with magnesium sulfate. After removing the desiccant, the solvent of the obtained solution was distilled off to obtain a pale yellow oil. Purification by recrystallization (hexane) gave N-Boc-propargylamine as a white solid (yield: 47.01 g, yield: 67.6percent).Propargylamine (5.50 g, 0.1 mol) and di-tert-butyl dicarbonate (4.36 g, 2 eq.) were suspended together in 100 mL of a 10percent aqueous solution of NaHCO14C. Prop-2-ynyl-carbamic acid tert-butyl ester; Di-fert-butyl dicarbonate (19.8g, 90.8 mmol) was dissolved in anhydrous dichloromethane (36 ml) and then added dropwise over 15 minutes to a solution of prop-2-ynylamine (6.22 ml, 90.8 mmol) in anhydrous dichloromethane (36 ml) at 0 To a solution of prop-2-yn-1-amine (245, 2.1 g, 38.2 mmol) in THF (30 mL) was added(Boc)20 (15 g, 68.8 mmol ). After stirring at room temperature for 1 h, the reaction mixturewas concentrated in vacuo to afford the residue, which was purified by column chromatography with a gradient elution of hexane (100percent) to hexane (80percent) and EtOAc (20percent) to provide tertbutyl prop-2-yn-1-ylcarbamate (246, 4.1 g, 26.4 mmol); ‘H NMR (300 MHz, CDC13): ö 4.70 (s, 1H), 3.85 (d, J= 3.0 Hz, 2H), 2.15 (t, J 2.7 Hz, 1H), 1.38 (s, 9H).Propargylamine hydrochloride (3.6 g, 39 mmol) and triethylamine (11.5 mL, 83 mmol, 2.13 equiv) were dissolved in CHPropargyl amine (9.6 g, 174.4 MMOL) was added dropwise to a solution of di-tert-butyl dicarbonate (46.1 g, 211.0 MMOL) in THF (70 mL). After 12 h the reaction was concentrated, the residue was dissolved in diethyl ether and washed with water (1 x) and brine (1 x). The organic layer was dried over NA2SO4 then concentrated to afford the title compound as a yellow oil (26 g, 97percent).

N-Boc-propargylamine is used in the preparation of triazolobenzylidene-thiazolopyrimidines which act as CDC25 phosphatase inhibitors. Also used in the synthesis of β-glucan polysaccharide analogs.

Molecular Weight:155.19
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:155.094628657
Monoisotopic Mass:155.094628657
Topological Polar Surface Area:38.3
Heavy Atom Count:11
Complexity:182
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes