Methanesulfonyl chloride → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-(N-(methylsulfonyl)methylsulfonamido) benzylcarbamoyloxy)ethyl)pyridine 1-oxide

HRID 1776464Notes

Reaction equation

[NH2:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][NH:7][C:8]([O:10][C@H:11]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]([F:31])[F:30])=[C:24]([O:32][CH2:33][CH:34]3[CH2:36][CH2:35]3)[CH:23]=2)[CH2:12][C:13]2[C:18]([Cl:19])=[CH:17][N+:16]([O-:20])=[CH:15][C:14]=2[Cl:21])=[O:9])=[CH:4][CH:3]=1.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>C(Cl)Cl>[Cl:19][C:18]1[CH:17]=[N+:16]([O-:20])[CH:15]=[C:14]([Cl:21])[C:13]=1[CH2:12][C@@H:11]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]([F:30])[F:31])=[C:24]([O:32][CH2:33][CH:34]2[CH2:36][CH2:35]2)[CH:23]=1)[O:10][C:8](=[O:9])[NH:7][CH2:6][C:5]1[CH:4]=[CH:3][C:2]([N:1]([S:40]([CH3:39])(=[O:42])=[O:41])[S:40]([CH3:39])(=[O:42])=[O:41])=[CH:38][CH:37]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of (S)-4-(2-(4-aminobenzylcarbamoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (190 mg, 0.334 mmol) and TEA (0.102 ml, 0.735 mmol) in DCM (7 ml) was cooled to 0° C., and methanesulfonyl chloride (0.051 ml, 0.669 mmol) was added. The cold bath was removed and the solution was stirred at RT for 5 hours. The reaction mixture was concentrated under reduced pressure and the resulting crude product (218 mg, 0.301 mmol, 90% yield, MS/ESI+ 646.3 [MH]+) was used in the next step without further purification.

Workup

customThe cold bath was removed
concentrationThe reaction mixture was concentrated under reduced pressure

Sources & evidence

ORD record: ord-2c78c22b214a425dac0f208c89d15e1a
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265768B2

Reaction notes

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