Sodium Hydroxide → N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide

HRID 1912330Notes

Reaction equation

HRID 1912330 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]2[O:14][C:13]([C:15]3[CH:23]=[C:22]([C:24]4[CH:25]=[C:26]([NH:32][S:33]([C:36]5[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=5[F:43])(=[O:35])=[O:34])[C:27]([O:30][CH3:31])=[N:28][CH:29]=4)[CH:21]=[C:20]4[C:16]=3[CH:17]=[N:18][N:19]4S(C3C=CC=CC=3)(=O)=O)=[N:12][CH:11]=2)[CH2:3]1.[OH-].[Na+]>C(O)(C)C>[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]2[O:14][C:13]([C:15]3[CH:23]=[C:22]([C:24]4[CH:25]=[C:26]([NH:32][S:33]([C:36]5[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=5[F:43])(=[O:34])=[O:35])[C:27]([O:30][CH3:31])=[N:28][CH:29]=4)[CH:21]=[C:20]4[C:16]=3[CH:17]=[N:18][NH:19]4)=[N:12][CH:11]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59564711N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide

Product 1

HCID 49783925N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamideYield 23.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide (105 mg, 0.140 mmol) was suspended in isopropanol (2 ml) and 2M sodium hydroxide (aq) (0.699 ml, 1.399 mmol) added. The reaction mixture was stirred at RT for 2 h, the solvent removed under a stream of nitrogen and the residue dissolved in water (1 ml) and acidified to pH˜6 by the addition of 2M hydrogen chloride (aq)(a black precipitate formed). The suspension was extracted with dichloromethane (3×2 ml) and the combined organics dried to give a brown solid. This was combined with the black precipitate which remained insoluble in the extraction, dissolved in MeOH:DMSO (1 ml, 1:1, v/v) and purified by MDAP (method A). The appropriate fractions were concentrated in vacuo to give the title compound as a white solid (20 mg).

Workup

  1. customthe solvent removed under a stream of nitrogen
  2. dissolutionthe residue dissolved in water (1 ml)
  3. additionacidified to pH˜6 by the addition of 2M hydrogen chloride (aq)(a black precipitate
  4. customformed)
  5. extractionThe suspension was extracted with dichloromethane (3×2 ml)
  6. customthe combined organics dried
  7. customto give a brown solid
  8. extractionremained insoluble in the extraction
  9. dissolutiondissolved in MeOH
  10. customDMSO (1 ml, 1:1, v/v) and purified by MDAP (method A)
  11. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-f66fe23bafd044a994981662222e5557
Source dataset
uspto-grants-2013_12
Patent number
US08609657B2

Reaction notes

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