Sodium Hydroxide → HCID 59200040, compound

HRID 2382038Notes

Reaction equation

HRID 2382038 reaction equation
C[O:2][C:3](=[O:33])[C:4]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[N:9]([NH:17][C:18]([C:20]2[C:21]([CH3:32])=[N:22][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:24][CH:25]=2)=[O:19])[CH:8]=1)([CH3:6])[CH3:5].[OH-].[Na+]>CO>[F:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]([NH:17][C:18]([C:20]1[C:21]([CH3:32])=[N:22][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:24][CH:25]=1)=[O:19])[CH:8]=[C:7]2[C:4]([CH3:6])([CH3:5])[C:3]([OH:33])=[O:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68554534HCID 68554534, compound

Product 1

HCID 59200040HCID 59200040, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-{5-fluoro-1-[(4-methyl-2-pyridin-2-yl-pyrimidine-5-carbonyl)-amino]-1H-indol-3-yl}-2-methyl-propionic acid methyl ester (0.85 mmol) in MeOH (5 mL) is treated with 10% aqueous NaOH (2 mL) and stirred at rt overnight. The mixture is then concentrated, diluted with EtOAc (50 mL), and extracted with 10% aqueous NaOH (3×50 mL). The aqueous layer is acidified with 12 M aqueous HCl, extracted with DCM (3×50 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated. The residue is triturated with Et2O to afford 2-[5-fluoro-1-[(4-methyl-2-pyridin-2-yl-pyrimidine-5-carbonyl)-amino]-1H-indol-3-yl]-2-methyl-propionic acid (100 mg, 27%, 3 steps). MS: 434 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 9.26 (s, 1H), 8.79 (m, 1H), 8.44 (d, 1H), 8.03 (t, 1H), 7.59 (m, 1H), 7.53 (s, 1H), 7.49 (m, 1H), 7.35 (d, 1H), 7.08 (t, 1H), 2.79 (s, 3H), 1.59 (s, 6H).

Workup

  1. concentrationThe mixture is then concentrated
  2. additiondiluted with EtOAc (50 mL)
  3. extractionextracted with 10% aqueous NaOH (3×50 mL)
  4. extractionextracted with DCM (3×50 mL)
  5. dry with materialThe combined organic layer is dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is triturated with Et2O

Sources & evidence

ORD record
ord-f1d7570957654471b37438dfc608c7c6
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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