Sodium Hydroxide → N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide

HRID 1695787Notes

Reaction equation

HRID 1695787 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([C:21]2[CH:29]=[C:28]3[C:24]([CH:25]=[N:26][N:27]3S(C3C=CC(C)=CC=3)(=O)=O)=[C:23]([NH:40][C:41]([C:43]3[N:44]=[C:45]([CH2:48][N:49]4[CH2:54][C@H:53]([CH3:55])[O:52][C@H:51]([CH3:56])[CH2:50]4)[S:46][CH:47]=3)=[O:42])[CH:22]=2)[CH:16]=[N:17][C:18]=1[O:19][CH3:20])(=[O:11])=[O:10].[OH-].[Na+]>CC(O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([C:21]2[CH:29]=[C:28]3[C:24]([CH:25]=[N:26][NH:27]3)=[C:23]([NH:40][C:41]([C:43]3[N:44]=[C:45]([CH2:48][N:49]4[CH2:50][C@H:51]([CH3:56])[O:52][C@H:53]([CH3:55])[CH2:54]4)[S:46][CH:47]=3)=[O:42])[CH:22]=2)[CH:16]=[N:17][C:18]=1[O:19][CH3:20])(=[O:10])=[O:11]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58255764N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide

Product 1

HCID 66692163N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamideYield 62.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-{6-[5-{[(2,4-Difluorophenyl)sulfonyl]amino}-6-(methyloxy)-3-pyridinyl]-1-[(4-methylphenyl)sulfonyl]-1H-indazol-4-yl}-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (105 mg) was dissolved in IPA (1 mL) and 2M NaOH (aq) (1 mL) and stirred at room temperature overnight. The IPA was evaporated and the remaining aqueous phase was diluted with water (2 ml), then acidified to ca. pH 4 using 2M HCl (aq) to give a precipitate that was extracted into DCM, passed through a hydrophobic frit, then evaporated to dryness. The residue was purified by ISCO companion 12 g silica cartridge using a 0-6% methanol in DCM gradient over 16 mins at 30 ml/min. Product containing fractions were combined, evaporated to dryness then further dried on a vacuum line to give title compound, (53 mg).

Workup

  1. customThe IPA was evaporated
  2. additionthe remaining aqueous phase was diluted with water (2 ml)
  3. customto give a precipitate that
  4. extractionwas extracted into DCM
  5. customevaporated to dryness
  6. customThe residue was purified by ISCO companion 12 g silica cartridge
  7. customover 16 mins
  8. additionProduct containing fractions
  9. customevaporated to dryness
  10. customthen further dried on a vacuum line

Sources & evidence

ORD record
ord-97ec11b56f2a4244a6dda85c4298547e
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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