Sodium hydride → Ethyl 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylate

HRID 1040117노트

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HRID 1040117 반응식
[H-].[Na+].[O:3]=[C:4]1[CH:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:7][CH2:6][NH:5]1.Br[CH2:15][C:16]1[S:17][C:18]([C:21]2[CH:22]=[C:23]([NH:28][C:29]3[N:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=3)[CH:24]=[C:25]([CH3:27])[CH:26]=2)=[CH:19][N:20]=1>O1CCCC1.C(OCC)(=O)C>[CH3:27][C:25]1[CH:26]=[C:21]([C:18]2[S:17][C:16]([CH2:15][C:8]3([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:7][CH2:6][NH:5][C:4]3=[O:3])=[N:20][CH:19]=2)[CH:22]=[C:23]([NH:28][C:29]2[N:34]=[C:33]([C:35]([F:37])([F:36])[F:38])[CH:32]=[CH:31][N:30]=2)[CH:24]=1

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 12699000Ethyl 2-oxopyrrolidine-3-carboxylateHCID 58456292N-{3-[2-(bromomethyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

생성물 1

HCID 58456303Ethyl 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylate수율 27%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

To sodium hydride in mineral oil (60%, 0.007 g, 0.33 mmol) was added tetrahydrofuran (1.8 mL) and the suspension was cooled to 0° C. Ethyl 2-oxopyrrolidine-3-carboxylate (0.044 g, 0.28 mmol) was added and the solution was stirred for 15 minutes. N-{3-[2-(bromomethyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (0.100 g, 0.23 mmol) was dissolved in tetrahydrofuran (1.8 mL) and then added to the flask. The reaction was allowed to warm to room temperature overnight. The reaction was diluted with ethyl acetate, washed carefully with water, dried over magnesium sulfate, filtered and concentrated. The solid was purified by silica gel chromatography to yield ethyl 3-{[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]methyl}-2-oxopyrrolidine-3-carboxylate (0.03 g, 27% yield). MS ESI: [M+H]+ m/z 505.7. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (d, J=5.2, 1H), 8.11 (s, 1H), 8.02-7.84 (m, 2H), 7.47 (s, 1H), 7.28 (d, J=5.2, 1H), 7.14 (s, 1H), 4.11 (q, J=7.4, 2H), 3.58 (in 1H), 3.28-3.21 (m, 2H), 3.15-3.03 (m, 1H), 2.66-2.54 (m, 1H), 2.31 (s, 3H), 2.27-2.16 (m, 1H), 1.15 (t, J=7.3, 3H). rhSYK activity=+++

후처리

  1. additionadded to the flask
  2. temperatureto warm to room temperature overnight
  3. washwashed carefully with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solid was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-85451202b489415ebf3cdb8ea2a3988a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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