Water → 4-Fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 453194Notes

Reaction equation

HRID 453194 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([CH2:24][O:25]C(=O)C)[N:19]=2)=[CH:15][CH:14]=[C:13]2[C:9]=1[CH:10]=[C:11]([CH3:42])[N:12]2[C:29](=[O:41])[NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=1.[NH4+].[Cl-].O>CO>[F:40][C:37]([F:38])([F:39])[C:33]1[CH:32]=[C:31]([NH:30][C:29]([N:12]2[C:13]3[C:9](=[C:8]([F:7])[C:16]([O:17][C:18]4[CH:23]=[CH:22][N:21]=[C:20]([CH2:24][OH:25])[N:19]=4)=[CH:15][CH:14]=3)[CH:10]=[C:11]2[CH3:42])=[O:41])[CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 59394198acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester

Product 1

HCID 593945384-Fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

Potassium carbonate (289 mg, 2.09 mmol) is added to a solution of acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester (1.05 g, 2.09 mmol) in MeOH (40 mL) at 23° C. The resulting mixture is stirred at 23° C. for 1 h. Saturated aqueous NH4Cl (50 mL) and water (20 mL) are added and the mixture is extracted with EtOAc (3×50 mL). The organic layers are combined, washed with brine (30 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (10-100% EtOAc/heptane) to provide 4-fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 461.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.02 (s, 1 H) 8.69 (d, J=5.56 Hz, 1 H) 8.12 (s, 1 H) 7.91 (s, 1 H) 7.66 (t, J=7.96 Hz, 1 H) 7.52 (t, J=8.34 Hz, 2 H) 7.17 (dd, J=8.84, 7.83 Hz, 1 H) 7.05 (d, J=5.56 Hz, 1 H) 6.63 (s, 1 H) 5.14 (t, J=6.19 Hz, 1 H) 4.38 (d, J=6.32 Hz, 2 H) 2.59 (s, 3 H).

Workup

  1. extractionthe mixture is extracted with EtOAc (3×50 mL)
  2. washwashed with brine (30 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel chromatography (10-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-ffba00771c2044e6ae455c689aa2dc4d
Source dataset
uspto-grants-2013_07
Patent number
US08492393B2

Reaction notes

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