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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 410626
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HRID 410626 반응식
[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
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참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

실험 절차

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=+++

후처리

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

출처 및 근거

ORD 기록
ord-7fdc61197d114ead974a2bf8cb3fde03
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08759366B2

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