Lithium Hydroxide → HCID 59199995, compound

HRID 2382022Notes

Reaction equation

HRID 2382022 reaction equation
C[O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([NH:14][C:15]([C:17]3[C:18]([CH3:30])=[N:19][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=4)=[N:21][CH:22]=3)=[O:16])[C:10]=2[CH:11]=[CH:12][CH:13]=1)=[O:4].[Li+].[OH-]>CO.C1COCC1.O.O>[F:29][C:25]1[CH:24]=[C:23]([C:20]2[N:19]=[C:18]([CH3:30])[C:17]([C:15]([NH:14][N:9]3[C:10]4[CH:11]=[CH:12][CH:13]=[C:5]([C:3]([OH:4])=[O:2])[C:6]=4[CH:7]=[CH:8]3)=[O:16])=[CH:22][N:21]=2)[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59199991HCID 59199991, compound

Product 1

HCID 59199995HCID 59199995, compoundYield 99.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A solution of 1-{[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-1H-indol-4-carboxylic acid methyl ester (0.48 mmol) and LiOH (1.91 mmol) in Methanol/THF/H2O (1:1:1, 6 mL) is stirred at rt overnight. The reaction mixture is diluted with water and washed with DCM. The aqueous layer is separated and acidified with 10% aqueous HCl to adjust pH to 1. The mixture is extracted with ether twice. The organic layer is dried (Na2SO4), filtered and concentrated in vacuo to afford 1-{[2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carbonyl]-amino}-1H-indol-4-carboxylic acid (186 mg, 99%) as a solid. MS: 391 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.85 (s, 3H), 7.20 (m, H), 7.24-7.40 (m, 2H), 7.46-7.61 (m, 2H), 7.66 (d, H), 7.92 (d, H), 8.23 (d, H), 8.37 (d, H), 9.16 (s, H).

Workup

  1. washwashed with DCM
  2. customThe aqueous layer is separated
  3. extractionThe mixture is extracted with ether twice
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-054df4f6d2e54d67b844c2dfd9273fac
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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