3-(Methylsulfonyl)-1-propanol

The alcohol 5-a (200 g, 1900 mmol) was dissolved in CHStep 1 : Synthesis of 3-(methylsulfonyl)propan-l-ol 12-a3-(methylthio)propan-l-ol (200 g, 1900 mmol, CAS 505-10-2) was dissolved in CHThe 3-(methylthio)propan-l-ol 6-a (200 g, 1900 mmol, CAS 505-10-2) was dissolved in CHThe alcohol 5-a (200 g, 1900 mmol) was dissolved in CHThe alcohol 23-a (200 g, 1900 mmol) was dissolved in CHStep 1 : Synthesis of 3-(methylsulfonyl)propan-1-ol23-bThe alcohol23-a (200 g, 1900 mmol) was dissolved in CH2Ch (2000 ml). The mixturewas cooled to 0°C. The m-CPBA 8Spercent in water (970 g, S700 mmol) was added portionwise keeping the temperature between 0 to S°C. After addition, the mixture was allowed to warm to 2S°C and stirred for 1S h. The mixture was filtered through a celitepad. The filtrate was purified by flash column (Eluent: petroleum ether: ethyl acetate =3:1 and then ethyl acetate: methanol= 10:1) to yield the intermediate 23-b (7S g, 29percent).Step 1: synthesis of 3-(methylsulfonyl)propan-1-ol (intermediate 14a)3-(methylthio)propan-1-ol (200 g, 1900 mmol, CAS 5 05-10-2) was dissolved inCH2C12 (2000 mL). The mixture was cooled to 0°C, then m-CPBA 85percent in water (970g, 5700 mmol, CAS 937-14-4) was added portion wise keeping the temperaturebetween 0 and 5°C. After addition, the mixture was allowed to warm to 25°C and stirred for 15 h. The mixture was filtered through a celite pad and the filtrate was purified by flash column (Eluent: petroleum ether: ethyl acetate = 3:1 and then ethyl acetate: methanol = 10:1) to yield the intermediate 14a (75 g, 29percent).The 3-(methylthio)propan-l-ol (200 g, 1900 mmol, CAS 505-10-2) was dissolved in CHThe alcohol 23-a (200 g, 1900 mmol) was dissolved in CH3-(Methylthio)propan-1-ol (200 g, 1900 mmol) was dissolved in CH2C12 (2000 mL).The mixture was cooled to 0°C, then m-CPBA 85percent in water (970 g, 5700 mmol) was added portion wise keeping the temperature between 0 and 5°C. After addition, the mixture was allowed to warm to 25°C and stirred for 15 hours. The mixture was filtered through a celite pad and the filtrate was purified by flash column (eluent:petroleum ether: ethyl acetate = 3:1 and then ethyl acetate: methanol = 10:1) to yield the intermediate (3a) (75 g, 29percent).The mixture of the compound 46 (2.00g), meta-chloroperbenzoic acid (9.40g), and a methylene chloride (60 mL) was stirred at the room temperature for 16 hours. Reaction mixed liquor was concentrated in vacuum after cerite filtration, silica gel column chromatography (eluate: chloroform/methanol =9/1) refined residue, and it obtained the compound 47 (0.660g).A solution of 3-(methylthio)-1-propanol (5.3 g, 50 mmol) in methanol (500 ml) was added to a solution of OXONE, (trade mark of E. I. du Pont de Nemours and Co., Inc), (30 g) in water (150 ml) and the mixture stirred at ambient temperature for 24 hours. The starting material was prepared as follows: B) To a solution of Compound A (1.05 g, 2.44 mmol) in dimethyl formamide (25 mL) at RT was added 3-(methylsulfonyl) propanol (0.75 g, 5.3 mmol). The mixture was stirred at [85 C] for 2 h, cooled and concentrated in vacuo. The residue was dissolved in dichloromethane and concentrated. The solid obtained was then triturated with dichloromethane several times to remove impurities. The resulting solid was treated with HCl in ether to obtain the salt of the title compound (0.9 g, 65%) as an off-white solid. LC/MS; (M+H) + = 541.3 Examples 24 and 25 Examples 24 and 25 were prepared from Example 22 by using a procedure similar to that for the preparation of Example 23.Compound WX037 (0.1 g, 220.03 mumol, 1 eq), 3-methanesulfonic acid-1-propanol (33.45 mg, 242.03 mumol, 1.1 eq), triphenylphosphine (86.57 mg, 330.05 mumol, 1.5 eq) were added into a 8 mL pre-dried reaction bottle, and then anhydrous tetrahydrofuran (7 mL) was added. The bottle was purged with nitrogen for 3 minutes, and then diisopropyl azodicarboxylate (66.74 mg, 330.05 mumol, 64.17 muL, 1.5 eq) was added slowly. The system was reacted at 25 C. for 1 hour. After the reaction was completed, the reaction solution was directly dried on a rotary evaporator to give a crude product, which was separated by flash chromatography (column: Agela Durashell C18 150*25 mm 5 mum; mobile phase: [water (10 mM NH4HCO3)-ACN]; B %: 25%-45%, 10.5 min) to give WX040. 1H NMR (400 MHz, DMSO-d6) delta ppm 0.67-0.77 (m, 2H) 0.78-0.89 (m, 2H) 1.48 (d, J=6.65 Hz, 6H) 1.85-1.94 (m, 1H) 2.19-2.31 (m, 2H) 3.02 (s, 3H) 3.18-3.28 (m, 2H) 4.39 (br t, J=6.27 Hz, 2H) 5.33 (quin, J=6.65 Hz, 1H) 7.35 (d, J=1.13 Hz, 1H) 7.49 (s, 1H) 7.90-7.94 (m, 1H) 7.94-8.00 (m, 1H) 8.11 (s, 1H) 8.24-8.30 (m, 2H) 8.74 (s, 1H) 8.95 (s, 1H).Methyl 7-cyclopropyi-6-hydroxypvrazolo[ I , 5-aipyridine-3-carboxvlate (0.075 g, 0.32 rnrnoi), 3-(methyisulfonyl)propan-1-oi (0.089 g, 0.65 rnrnoi), and 1, 1-(azodicarbonyl)dipiperidine (0.244 g, 0.969 mniol) were placed in a pressure vial. Then. PhMe (4 mL) and tri-N-butyiphosphine (0242 mL. 0969 mmoi) were added, and the reaction mixture was stirred at 140 C under microwave irradiation for 15 mir. The reaction mixture was quenched with MeOH (5 mL), diluted with MeOH/DCM (20 mL).and the solvent was removed under reduced pressure. The residue was purified by flash chromatography (0-75% EtOAc/DCM gradient) to give methyl 7-cyclopropyi-6-(3- (methyisuifonyl)propoxy)pyrazoio[i , 5-a]pyridine-3-carboxviate (0.094 g, 83 % yield) as a white solid. MS (ESI) rn/b: 353.1 (M-FH). 1H-NMR: (500 'll-lz, CDCI3) 3 ppm 8.40 (s. IH). 802 (d, J:::9 6 Hz. 1FI), 7.29 - 7.24 (in, 11-1), 4.21 (t. J:::59 Hz, 2H), 3.91 (s, 3H), 334 - 3.25 (m, 2H), 3.00 (s, 3H), 2.49 - 2.43 (m, 1H), 243 - 2.36 (m, 2H), 1.41 - 1.35 (m, 2H), 1.22 - 1.17 (m, 2H).General procedure: Under nitrogen atmosphere, to a 0 C solution of 18 (1.0 equiv.) and triphenylphosphine (1.2 equiv) in dry THF (3.0 mL), desired alcohol (1.2 equiv.) was added. Subsequently DEAD (solution 40% in toluene, 1.2 equiv.) was added dropwise. The mixture was left stirring under nitrogen at 0 C for 30 min and at room temperature for 3 hours. The solvent was removed under reduced pressure, and the resulting crude product extracted with EtOAc (3.0 mL), washed first with a saturated NH4Cl aqueous solution (3.0 mL) and then with a saturated NaHCO3 aqueous solution (3 x 3.0 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness. The crude product was purified either by column chromatography using a Teledyne ISCO apparatus or preparative HPLC to afford the corresponding N-O-alkyl substituted beta-lactams.To a solution of To a solution of 3-methylsulfonylpropan-l-ol (200 mg, 1.45 mmol) in DCM (5 mL) was added Et3N (732 mg, 23.5 mmol) and methanesulfonyl chloride (2.84 g, 24.9 mmol). The mixture was stirred at 30 C for 12 hrs, and then partitioned between H20 (20 mL) and DCM (60 mL). The organic layer was separated, washed with brine (50 mL), dried over anhydrous Na2S04 and concentrated under reduced pressure to afford crude 3-methylsulfonylpropyl methane sulfonate (300 mg) as a yellow oil, which was used directly in the next step without further purification.The mixture of the compound 47 (0.100g), methanesulfonyl chloride (0.067 mL), triethylamine (0.120 mL), and a methylene chloride (2.0 mL) was stirred at the room temperature for 1 hour. Water was added to reaction mixed liquor and ethyl acetate extracted. The organic layer was concentrated in vacuum and the rough product of the title compound 48 was obtained. The whole quantity was then used to the next reaction.Compound 1-18To a solution of 3-(methylsulfonyl)propan-l-ol (67 mg, 3 equiv.) in THF (803 mu), was added 1.0 M solution of LiHMDS in THF (482 mu, 3 equiv.). To this mixture, was added Intermediate -2 (60 mg, 1 equiv.). The mixture was stirred at rt for 24 h. The mixture was diluted in ethyl acetate (100 ml) and washed with water (50 ml). The organic layer was dried, filtered and evaporated to give an oil. The oil was purified by column chromatography (0 to 80% ethyl acetate in hexanes) to give the desired product (31 mg, 41 % yield) as a white solid.Under an argon atmosphere, 3-methyl sulfone-propanol (200mg, 1. 447mmol) and 4-iodophenol (382mg, 1. 737mmol) was dissolved in 10ml anhydrous tetrahydro-furans in Misaki, 0 C under stirring successively added triphenylphosphine (569mg, 2 · 171mmol) and diethyl azodicarboxylate (378mg, 2. 171mmol), the reaction 1 h, Tau1Chi (RhoEpsilon / EpsilonAlpha = 2/1) to detect material completion of the reaction, spin dry solution , column chromatography (PE / EA = 5 / 1-2 / 1), to give a white solid 400mg, yield 81.3%.

Molecular Weight:138.19
XLogP3:-0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:138.03506535
Monoisotopic Mass:138.03506535
Topological Polar Surface Area:62.8
Heavy Atom Count:8
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes