N-(4-mercaptophenyl)methanesulfonamide → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)phenylthio)carbonyloxy)ethyl)-pyridine 1-oxide

HRID 1776473Notes

Reaction equation

HRID 1776473 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].[SH:40][C:41]1[CH:46]=[CH:45][C:44]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])=[CH:43][CH:42]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:38][C:6]1[CH:5]=[N+:4]([O-:39])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:31])[F:32])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11]([S:40][C:41]1[CH:42]=[CH:43][C:44]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])=[CH:45][CH:46]=1)=[O:12]

Participants

5

Reactant 2

HCID 15615418N-(4-mercaptophenyl)methanesulfonamideHCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide

Product 1

HCID 71542823(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)phenylthio)carbonyloxy)ethyl)-pyridine 1-oxideYield 36.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbonyloxy)ethyl)pyridine 1-oxide (prepared with an analogous procedure to that described in Scheme 3, Step 1), (200 mg, 0.342 mmol) in DCM (10 ml), DMAP (41.7 mg, 0.342 mmol), and N-(4-mercaptophenyl)methanesulfonamide (83 mg, 0.410 mmol) were sequentially added. The mixture was stirred at RT for 4 hours, then the solvent was removed and the crude purified by flash chromatography on silica gel (DCM:MeOH 10:0.2). The resulting product was further purified by flash chromatography on silica gel (EtOAc:DCM 8:2) and the desired product was obtained (81 mg, 0.125 mmol, 36.5% yield, MS/ESI+ 649.28 [MH]+, [αD]=−59.64, c=0.44 in DCM).

Workup

  1. customthe solvent was removed
  2. customthe crude purified by flash chromatography on silica gel (DCM:MeOH 10:0.2)
  3. customThe resulting product was further purified by flash chromatography on silica gel (EtOAc:DCM 8:2)

Sources & evidence

ORD record
ord-637553320f974ad6aae9c7aa6ecf2082
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

Loading…