Water → (5-{3-[[5-fluoro-2-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-1H-indol-1-yl)acetic acid

HRID 2424990Notes

Reaction equation

HRID 2424990 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:15][CH2:16][CH2:17][N:18]([C:20]3[C:25]([F:26])=[CH:24][N:23]=[C:22]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[N:21]=3)[CH3:19])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.O.[OH-].[Li+]>CO.C1COCC1>[F:26][C:25]1[C:20]([N:18]([CH3:19])[CH2:17][CH2:16][CH2:15][O:14][C:10]2[CH:9]=[C:8]3[C:13](=[CH:12][CH:11]=2)[N:5]([CH2:4][C:3]([OH:35])=[O:2])[CH:6]=[CH:7]3)=[N:21][C:22]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[N:23][CH:24]=1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 57845456methyl (5-{3-[[5-fluoro-2-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-1H-indol-1-yl)acetate

Product 1

HCID 57845382(5-{3-[[5-fluoro-2-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-1H-indol-1-yl)acetic acidYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl(5-{3-[[5-fluoro-2-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-1H-indol-1-yl)acetate (Example 86, 0.1 g, 0.20 mmol) in methanol (2 mL), THF (2.00 mL), and water (1.00 mL) was added lithium hydroxide (0.05 g, 1.99 mmol). The mixture was stirred at rt for 18 h and then concentrated under reduced pressure. The residue was taken up in water and washed with ether. The aqueous layer was acidified to pH 3.5 and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give the title compound (0.092 g, 100%). 1H NMR (300 MHz, CD3OD) δ 8.20-8.17 (m, 2H), 8.03-8.01 (m, 1H), 7.18-6.78 (m, 6H), 6.33-6.30 (m, 1H), 4.74 (s, 2H), 4.11 (t, 2H), 3.94 (t, 2H), 3.83 (s, 3H), 3.36-3.34 (m, 3H), 2.26-2.20 (m, 2H). LC/MS m/z 465.2 (M+H)+, RT 2.51 min.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with ether
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-25f8675ae4aa4d5d920f27e4ef847969
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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