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

HRID 1776481Notes

Reaction equation

HRID 1776481 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[C:10]([SH:12])[CH:9]=[CH:8][C:7]=2[NH:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH2:3][CH2:2]1.[Cl:18][C:19]1[CH:20]=[N+:21]([O-:56])[CH:22]=[C:23]([Cl:55])[C:24]=1[CH2:25][C@@H:26]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)[O:27][C:28](OC1C=CC([N+]([O-])=O)=CC=1)=[O:29]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:55][C:23]1[CH:22]=[N+:21]([O-:56])[CH:20]=[C:19]([Cl:18])[C:24]=1[CH2:25][C@@H:26]([C:40]1[CH:45]=[CH:44][C:43]([O:46][CH:47]([F:49])[F:48])=[C:42]([O:50][CH2:51][CH:52]2[CH2:54][CH2:53]2)[CH:41]=1)[O:27][C:28]([S:12][C:10]1[CH:9]=[CH:8][C:7]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[CH:11]=1)=[O:29]

Participants

5

Reactant 2

HCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxideHCID 86679432N-(2-(cyclopropylmethoxy)-4-mercaptophenyl)methanesulfonamide

Product 1

HCID 71542824(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((3-(cyclopropylmethoxy)-4-(methylsulfonamido)-phenylthio)carbonyloxy)ethyl)pyridine 1-oxide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-(2-(cyclopropylmethoxy)-4-mercaptophenyl)-methanesulfonamide (0.112 g, 0.410 mmol), (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) (0.200 g, 0.342 mmol), and DMAP (0.021 g, 0.171 mmol) in DCM (8 ml) was stirred at RT overnight. The mixture was diluted with DCM and washed several times with diluted aqueous K2CO3. The organic layer was dried over Na2SO4 and the solvent was removed. The crude was purified by filtration on silica gel cartridge (DCM:EtOAc=80:20) affording the desired compound as a pale yellow amorphous solid. The product was further purified by flash chromatography on silica gel cartridge (petroleum ether:EtOAc=50:50 to 35:65) and by preparative LC/MS affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((3-(cyclopropylmethoxy)-4-(methylsulfonamido)phenylthio)carbonyloxy)ethyl)pyridine 1-oxide as an off-white amorphous solid (0.060 g, 0.083 mmol, 24.40% yield, MS/ESI+ 719.23 [MH]+, [αD]=−64.64, c=0.47 in DCM).

Workup

  1. washwashed several times with diluted aqueous K2CO3
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was removed
  4. filtrationThe crude was purified by filtration on silica gel cartridge (DCM:EtOAc=80:20)

Sources & evidence

ORD record
ord-f31d73e329ac4591b44318a2ddc6ef6f
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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