HCID 11592439, compound → HCID 11520153, compound

HRID 907611Notes

Reaction equation

HRID 907611 reaction equation
[C:1]([C:3]1([NH:9][C:10](=[O:40])[C@@H:11]([NH:20][C@@H:21]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:22]([F:32])([F:31])[O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:12][S:13]([CH2:16][CH:17]2[CH2:19][CH2:18]2)(=[O:15])=[O:14])[CH2:8][CH2:7]S[CH2:5][CH2:4]1)#[N:2].OO[S:43]([O-:45])=[O:44].[K+]>CO.O>[C:1]([C:3]1([NH:9][C:10](=[O:40])[C@@H:11]([NH:20][C@@H:21]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:22]([F:32])([F:31])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[CH2:12][S:13]([CH2:16][CH:17]2[CH2:19][CH2:18]2)(=[O:15])=[O:14])[CH2:4][CH2:5][S:43](=[O:45])(=[O:44])[CH2:7][CH2:8]1)#[N:2]

Participants

5

Reactant 2

HCID 11592439HCID 11592439, compoundHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 11520153HCID 11520153, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of N-(4-cyanotetrahydrothiopyran-4-yl)-3-cyclopropylmethanesulfonyl-2(R)-[2,2-difluoro-2-(4-fluorophenoxy)-1(S)-(4-fluorophenyl)ethylamino]propionamide (0.063 g, 0.1 mmol) in MeOH (10 ml) at 45° C., a solution of OXONE (0.3 mmol) in water (1 ml) was added. After stirring for 3 h at 45° C., the solvent was evaporated under vacuum and the residue was partitioned between DCM (15 ml) and water (15 ml). The organic phase was separated and the aqueous solution was extracted with DCM. The combined organic layers were washed with brine and dried over sodium sulfate. After removal of the solvent under vacuum, the crude was purified by preparative TLC, using ethyl acetate/hexanes (1/1) as mobile phase to give the title compound as a white solid (55%). 1HNMR (DMSO-d6): δ 8.82 (1H, s), 7.47 (2H, dd), 7.17 (6H, m), 4.32 (1H, q), 3.96 (1H, m), 3.40 (1H, m), 3.37 (4H, m), 3.00 (2H, m), 2.37 (2H), 1.15 (2H, m), 0.59 (3H, m), 0.30 (3H, m). LC/MS, M+1: 632.5; M−1: 630.6.

Workup

  1. customthe solvent was evaporated under vacuum
  2. customthe residue was partitioned between DCM (15 ml) and water (15 ml)
  3. customThe organic phase was separated
  4. extractionthe aqueous solution was extracted with DCM
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customAfter removal of the solvent under vacuum
  8. customthe crude was purified by preparative TLC

Sources & evidence

ORD record
ord-c38c13b8afbd4119a868b993d953d828
Source dataset
uspto-grants-2011_09
Patent number
US08013186B2

Reaction notes

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