Methanesulfonyl chloride → HCID 71542914, compound

HRID 1776644Notes

Reaction equation

HRID 1776644 reaction equation
[NH2:1][C:2]1[CH:39]=[CH:38][C:5]([CH2:6][N:7]([CH3:37])[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.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>N1C=CC=CC=1.C(Cl)Cl.[NH4+].[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[CH2:35][CH2:36]2)[CH:23]=1)[O:10][C:8](=[O:9])[N:7]([CH3:37])[CH2:6][C:5]1[CH:38]=[CH:39][C:2]([NH:1][S:41]([CH3:40])(=[O:43])=[O:42])=[CH:3][CH:4]=1

Participants

6

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 71542820HCID 71542820, compound

Product 1

HCID 71542914HCID 71542914, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-4-(2-((4-aminobenzyl)(methyl)carbamoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (for reference procedure see Example 3, Table 5) (73.2 mg, 0.126 mmol) was dissolved in pyridine (3 ml) and cooled at 0° C. Methanesulfonyl chloride (13.71 μl, 0.176 mmol) was added, and the reaction was stirred RT for 1 hour. The reaction was diluted with DCM and aqueous sat. NH4Cl. The aqueous phase was extracted twice with DCM, the combined organic layers were dried and evaporated. The residue was purified by flash chromatography on silica gel cartridge (DCM/AcOEt=80/20 to 50/50) to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(methyl(4-(methylsulfonamido)benzyl)carbamoyloxy)ethyl)pyridine 1-oxide (69 mg, 0.104 mmol, 83% yield, MS/ESI+ 660.0 [MH]+.

Workup

  1. extractionThe aqueous phase was extracted twice with DCM
  2. customthe combined organic layers were dried
  3. customevaporated
  4. customThe residue was purified by flash chromatography on silica gel cartridge (DCM/AcOEt=80/20 to 50/50)

Sources & evidence

ORD record
ord-03a0896de50044199b9d7c7786b3b91c
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

Loading…