1H-Pyrrol-1-amine

Step 2: lH-pyrrol-1 -amine[00158] To a solution of 2-(lH-pyrrol-l-yl)isoindoline-l, 3-dione (3.5 g, 0.016 mmol) in MeOH (35mL) was added hydrazine monohydrate (lmL, 0.021 mmol). The reaction mixture was heated to 65 °C for 1 h then was cooled and filtered. The resulting solid was rinsed with MeOH and the resulting filtrate was concentrated to give a light yellow solid which was triturated with diethyl ether. The organic solution was then concentrated to give 1 g (74percent) of a brown oil as the title compound. To a solution of 2-(lH-pyrrol-l-yl)isoindoline-l, 3-dione (3.5 g, 0.016 mmol) in methanol (35mL) was added hydrazine monohydrate (lmL, 0.021 mmol). The reaction mixture was heated to 65 °C for 1 h then was cooled and filtered. The resulting solid was rinsed with methanol and the resulting filtrate was concentrated to give a light yellow solid which was triturated with diethyl ether. The organic solution was then concentrated to give 1 g (74percent) of a brown oil as the title compound. (Step 3) N-aminopyrrole; Hydrazine monohydrate (8.8 ml, 144.8 mmol) was added to a solution of 1-phthalimidopyrrole (25.6 g, 120.6 mmol) in methanol (500 mL) and stirred for 1 hour under reflux. The resulting reaction mixture was cooled to room temperature and stirred for 15 minutes under reflux after cautiously adding acetic acid. The resulting solution was filtered and methanol was removed by distillation. The resulting residue was extracted with dichloromethane after adding 40percent sodium hydroxide aqueous solution. Then, the extract was concentrated and the remaining residue was purified by vacuum distillation. The target compound was yielded (6.5 g, 79.2 mmol, 66percent yield).This product was dissolved in 60 ml of methanol and 3 ml of 82% hydrazine hydrate was slowly added thereto. After refluxing the reaction mixture for 30 min, cooled to 0~5 C. and 1.5 ml of glacial acetic acid was added thereto. The resulting precipitate was filtered off and the filtrate was concentrated under the reduced pressure to remove methanol. The concentrate was washed with diethyl ether and vacuum-distilled to give 2.4 g of the desired compound(47.3%). bp=71~73 C. (12 mmHg) NMR (CDCl3, delta) 4.5 (s, 2H, NH2), 5.89 (t, 2H) 6.40 (t, 2H)The azide (30 mg, 0.11 mmol) from Step B was dissolved in MeOH (2 mL) and treated with 10% Pd/C (15 mg), and shaken at 30 PSI under hydrogen for 30 minutes. The reaction mixture was filtered thru Celite, washed with MeOH (3*25 mL), and concentrated in vacuo. The residue was purified by column chromatography (2 g silica gel 60, 10 mm diam. column, 2.5-5% MeOH/CH2 Cl2) to afford the amino pyrrole (10 mg, 36%). 1 H NMR (CDCl3, 500 MHz) delta 7.21-7.42 (m, 5H), 6.50 (d, 2H, J=1.8 Hz), 6.11 (d, 2H, J=1.9 Hz), 3.86 (d, 1H, J=13.9 Hz), 3.46-3.50 (m, 1H), 3.17 (s, 1H), 2.56 (bs, 2H), 1.55-1.85 (m, 8H) ppm.Preparation of Step two:-Preparation of Reference Synthesis Synthesis of (0.50 g, 6.1 mmol) was dissolved in 3:1 MeOH:AcOH (16 mL) at room temperature after which 2-chloromalonaldehyde (0.78 g, 7.3 mmol) was added. The resulting mixture was stirred at room temperature for 30 min. then heated to 80 C. for 16 hrs. The solvents were removed by rotary evaporation and the crude residue partitioned between water and EtOAc. The layers were separated and the aqueous layer was extracted once with EtOAc. The organic layers were combined, dried with MgSO4, filtered and concentrated. The crude residue was then purified via silica gel chromatography (eluent: EtOAc/hexanes) to give the product 3-chloropyrrolo[1, 2-b]pyridazine (I-2). 1H NMR (400 MHZ, CHLOROFORM-D) Delta 7.93 (D, J=2.5 HZ, 1H), 7.75-7.70 (M, 1H), 7.69 (D, J=2.5 HZ, 1H), 6.86 (DD, J=4.3, 2.8 HZ, 1H), 6.45 (DD, J=4.3, 1.4 HZ, 1H).A stirred suspension of 3, 3-diethoxy-2-formylpropionitrile potassium salt (I-1C, 5.10 g, 24.36 mmol) was cooled to 0 C., and concentrated HCl (7.11 mL, 85.26 mmol) was added dropwise at such a rate that the internal temperature of the reaction did not go above 20 C. After addition was complete, the reaction was stirred at room temperature for 20 minutes. To this reaction mixture was added a solution of A stirred suspension of 3, 3-diethoxy-2-formylpropionitrile potassium salt (I-1C, 5.10 g, 24.36 mmol) was cooled to 0 C., and concentrated HCl (7.11 mL, 85.26 mmol) was added dropwise at such a rate that the internal temperature of the reaction did not go above 20 C. After addition was complete, the reaction was stirred at room temperature for 20 minutes. To this reaction mixture was added a solution of A stirred suspension of 3, 3-diethoxy-2-formylpropionitrile potassium salt (I-1C, 5.10 g, 24.36 mmol) was cooled to 0 C, and concentrated HC1 (7.11 mL, 85.26 mmol) was added dropwise at such a rate that the internal temperature of the reaction did not go above 20 C.After addition was complete, the reaction was stirred at room temperature for 20 minutes. To this reaction mixture was added a solution of l-aminopyrrole (I- ID, 1.00 g, 12.18 mmol) in methanol (4.0 mL). After addition, the reaction mixture was refluxed at 90 C for 2 hours. When heating was complete, the reaction was cooled to room temperature and concentrated to about half of the original volume. Saturated aqueous sodium bicarbonate was added carefully to the resulting residue until bubbling stopped. The solution was extracted with two portions of ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, concentrated in vacuo, and the resulting residue was purified by silica gel chromatography (eluent:EtO Ac/hexanes) to provide I-1E.1H NMR (400 MHz, Chloroform-ri) d 8.16 - 8.03 (m, 2H), 7.93 (ddd, J = 2.6, 1.4, 0.6 Hz, 1H), 7.04 (dd, J = 4.5, 2.7 Hz, 1H), 6.84 (dd, J = 4.6, 1.4 Hz, 1H).A stirred suspension of 3, 3-diethoxy- 2-formylpropionitrile potassium salt (I-8C, 5.10 g, 24.36 mmol) was cooled to 0 C, and concentrated HC1 (7.11 mL, 85.26 mmol) was added dropwise at such a rate that the internal temperature of the reaction did not go above 20 C. After addition was complete, the reaction was stirred at room temperature for 20 minutes. To this reaction mixture was added a solution of A stirred suspension of 3, 3-diethoxy-2-formylpropionitrile potassium salt (I-1C, 5.10 g, 24.36 mmol) was cooled to 0 C., and concentrated HCl (7.11 mL, 85.26 mmol) was added dropwise at such a rate that the internal temperature of the reaction did not go above 20 C. After addition was complete, the reaction was stirred at room temperature for 20 minutes. To this reaction mixture was added a solution of To a solution of

Molecular Weight:82.10
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:82.053098200
Monoisotopic Mass:82.053098200
Topological Polar Surface Area:31
Heavy Atom Count:6
Complexity:38.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes