Sodium hydride → 2-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-6-methyl-4a,7a-dihydro-3H-thieno[2,3-d]pyrimidin-4-one

HRID 1752268노트

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HRID 1752268 반응식
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.Cl[CH2:24][C:25]1[NH:26][C:27](=[O:35])[C:28]2[CH:33]=[C:32]([CH3:34])[S:31][C:29]=2[N:30]=1.[H-].[Na+]>C1COCC1.CCOCC>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:19][CH2:18][N:17]([CH2:24][C:25]4[NH:26][C:27](=[O:35])[CH:28]5[CH:33]=[C:32]([CH3:34])[S:31][CH:29]5[N:30]=4)[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:21][CH:22]=1

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 64916832-(Chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-oneHCID 712122103-(4-(4-Methoxybenzoyl)piperidin-1-yl)pyrrolidin-2-one

생성물 1

HCID 712122132-{3-[4-(4-Methoxy-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-ylmethyl}-6-methyl-4a,7a-dihydro-3H-thieno[2,3-d]pyrimidin-4-one수율 95.4%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

To a solution of 3-[4-(4-methoxy-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (0.165 mmol, 50 mg) and 2-chloromethyl-6-methyl-3H-thieno[2,3-d]pyrimidin-4-one (0.165 mmol, 33 mg) in THF (2 mL) was added sodium hydride (60%, 0.331 mmol, 23 mg) and heated to 70° C. for 1 hour. The reaction was allowed to cool to ambient temperature, diluted with 10 mL of ether, and the resulting solid in suspension was filtered and dried under vacuum provided the title compound as an off-white solid (70.5 mg, 95.4% yield). HRMS calculated for C25H28N4O4S 480.5903. found (ESI, [M+H]+) 481.1907. 1H NMR (400 MHz, MeOD) δ ppm 1.66-1.93 (m, 4H) 2.05-2.30 (m, 2H) 2.51-2.63 (m, 1H) 2.79-2.90 (m, 1H) 2.90-2.98 (m, 1H) 3.03-3.18 (m, 1H) 3.33-3.54 (m, 4H) 3.65-3.75 (m, 1H) 3.87 (s, 3H) 4.20-4.31 (m, 1H) 4.51-4.62 (m, 1H) 6.94-7.06 (m, 3H) 7.98 (d, J=9.03 Hz, 2H), analytical RP-HPLC retention time=3.22 min

후처리

  1. temperatureto cool to ambient temperature
  2. filtrationthe resulting solid in suspension was filtered
  3. customdried under vacuum

출처 및 근거

ORD 기록
ord-3c663871a7c24b0291a60a9bb14d4a7d
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163003B2

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