1-(Diphenylmethyl)-3-[(methylsulfonyl)oxy]azetidine

White Crystalline Solid

Methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (12) (Scheme 5, step 8). To a solution of 1-benzhydryl-azetidin-3-ol (15.0 g, 62.7 mmol) in dry CHStep 1: l-Benzhydrylazetidin-3-yl methanesulfonateTriethylamine (870 ml, 62.67 mmol) and mesyl chloride (390 μΙ_, 50.13 mmol) were successively added to a solution of l-benzhydrylazetan-3-ol (1.0 g, 41.78 mmol) in dichloromethane (10 mL) at room temperature. The reaction mixture was stirred for 1 hour and then diluted by addition of water (20 mL). The aqueous phase was separated and extracted with dichloromethane (2 x 40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (40 mL), dried over sodium sulfate, filtered and concentrated to dryness. The title compound was obtained as a yellow solid (1.5 g, 100percent).*H NMR (CDCIExample 38 A mixture of 1-benzhydrylazetidin-3-ol (20.0 g, 83.68 mmol) and Et3N (12.68 g, 125.52 mmol) in DCM (200 mL) at 0°C, MsC1 (11.447 mg, 100.41 mmol) was added in portions and the resulting solution was stirred at RT for 1 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer wasdried over anhydrous Na2504, filtered and concentrated in vacuo to afford the desired product (26.526 g, 100percent yield).Example 8 N-(4-{4-[3-(4-hydroxymethylpiperidin-1-yl)azetidin-1-yl]phenylamino}-6-methoxypyridin-3-yl)acetamide (8a) 1-benzhydrylazetidin-3-yl methanesulfonate 1-Benzhydrylazetidin-3-ol (30.0 g, 125 mmol) was dissolved in methylene chloride (240 mL), triethylamine (26 mL, 0.19 mol) was added and, under ice-cooling, methanesulfonyl chloride (11.6 mL, 150 mmol) was added, and the mixture was stirred for 1.5 hr. Water (100 mL) was added, two layers were separated, and the organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title object compound as a pale-yellow powder (40.1 g, yield 100percent). A solution of methanesulfonyl chloride (115 g, 1.01 mol) in CHTo a stirred solution of l-benzhydrylazetidin-3-ol (4.0 g, 16.7 mmol, CAS 18621-17-5) in CHStep 2To a suspension of l-benzhydrylazetidin-3-ol [93] (5.0 g, 2 mmol) in DCM (50 ml), pyridine (8.26ml, 10 mmol) were slowly added at 0°C under inert atmosphere. After the addition was complete, the suspension dissolved was stirred at 0 °C for 20 min, then methane sulphonyl chloride (2.5 ml, 15 mmol) was added to the solution and stirred at RT for 2 h. The progress of the reaction was monitored by TLC. Reaction mixture was quenched with water (150 ml) and extracted with DCM (500 ml x 2). The DCM layer was washed with brine (100 ml x 2), dried over anhydrous Na(Production Example 81) 1-Benzhydryl-3-(methanesulfonyloxy)azetidine Water (7.2 ml) and sodium cyanate (3.48 g) were added to a solution of 1-benzhydryl-3-(methanesulfonyloxy)azetidine (7.52 g) in N, N-dimethylformamide (60 ml), followed by stirring at 65° C. for 9 hours. Water, sodium carbonate and ethyl acetate were added to the reaction mixture, which was partitioned. The aqueous layer was extracted with ethyl acetate. The organic layer was collected, washed with brine, and dried over anhydrous sodium sulfate. This was concentrated under reduced pressure, and the resultant crystals were suspended by addition of diethyl ether (10 ml). The crystals were collected by filtration, and washed with diethyl ether. This was dried under aeration to give the title compound (5.43 g, 92.3percent) as pale yellow crystals.(Reference Example F-1) 1-Benzhydryl-3-(methanesulfonyloxy)azetidine To a cooled solution of 1-Benzhhydrylazetidin-3-ol (3.5 g, 14.624 mmol, available from Manchester A10473) and triethylamine (4.07 ml, 29.25 mmol) in toluene (21 ml) Methanesulfonyl chloride (1.13 ml, 14.62 mmol) was added dropwise keeping the temperature at 0° C. The reaction mixture was stirred 1 h at 0° C. then the solid was filtered off and washed with toluene (2×5 ml). The yellow filtrate was evaporated in vacuo to afford the title compound (D19) (5g).C. [Referential Example 103]; (1-Benzhydrylazetidin-3-yl) methanesulfonate ; Under cooling with ice, methanesulfonyl chloride (0.68 mL) was added dropwise to 1-benzhydrylazetidin-3-ol (1.50 g) in pyridine (12 mL), followed by stirring at room temperature overnight. Ice-water was added to the reaction mixture, and the precipitated material was recovered by filtration, to thereby give the title compound (890 mg, 45percent). LC-MSm/z: 318(M+H)+.

A proline analog and proline formation inhibitor

Molecular Weight:317.4
XLogP3:2.7
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:317.10856464
Monoisotopic Mass:317.10856464
Topological Polar Surface Area:55
Heavy Atom Count:22
Complexity:423
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes