Methanol → 3-{[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylic acid

HRID 1040118Notes

Reaction equation

HRID 1040118 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH2:24][C:25]3([C:31]([O:33]CC)=[O:32])[CH2:29][CH2:28][NH:27][C:26]3=[O:30])=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.O1CCCC1.CO.[OH-].[Li+]>C(OCC)(=O)C.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([CH2:24][C:25]3([C:31]([OH:33])=[O:32])[CH2:29][CH2:28][NH:27][C:26]3=[O:30])=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 58456303Ethyl 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylate

Product 1

HCID 584561223-{[5-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylic acidYield 66.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To ethyl 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylate (0.032 g, 0.063 mmol) was added tetrahydrofuran (0.3 mL), methanol (0.16 mL) and water (0.16 mL). Lithium hydroxide (0.003 g, 0.13 mmol) was added and the reaction was stirred at room temperature. Once complete, the reaction was diluted with ethyl acetate, washed with hydrochloric acid (1N in water), dried over magnesium sulfate, filtered and concentrated to yield 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylic acid (0.02 g, 66%) without further purification. MS ESI: [M+H]+ m/z 477.7. 1H NMR (500 MHz, CD3OD) δ 8.71 (d, J=5.2, 1H), 7.97 (s, 1H), 7.89 (s, 1H), 7.45 (s, 1H), 7.16-6.98 (m, 2H), 3.67 (m, 1H), 3.54-3.39 (m, 2H), 3.24-3.13 (m, 1H), 2.70-2.52 (m, 1H), 2.36 (s, 3H), 2.00 (d, J=10.4, 1H). rhSYK activity=+++

Workup

  1. washwashed with hydrochloric acid (1N in water)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7801442caf33431b9201cbe0b2e97a12
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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