Diisopropylethylamine → N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-1-methyl-3-oxo-2-phenyl-5-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 2359671노트

반응식

HRID 2359671 반응식
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:13][C:14]3[CH:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=3)=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.[CH3:21][N:22]1[C:26]([CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)=[C:25]([C:33](O)=[O:34])[C:24](=[O:36])[N:23]1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([O:13][C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:33]([C:25]4[C:24](=[O:36])[N:23]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=5)[N:22]([CH3:21])[C:26]=4[CH2:27][N:28]4[CH2:29][CH2:30][CH2:31][CH2:32]4)=[O:34])=[N:18][CH:19]=3)=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595983945-(7-Methoxyquinolin-4-yloxy)pyridin-2-amineHCID 595984571-methyl-3-oxo-2-phenyl-5-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1H-pyrazole-4-carboxylic acid

생성물 1

HCID 11947782N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-1-methyl-3-oxo-2-phenyl-5-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1H-pyrazole-4-carboxamide수율 8%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

5-(7-methoxy-quinolin-4-yloxy)pyridin-2-amine (549 mg, 2.05 mmol) and 1-methyl-3-oxo-2-phenyl-5-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1H-pyrazole-4-carboxylic acid (696 mg, 2.31 mmol) were suspended in dichlormethane (10 ml) and N-ethyl-N-isopropylpropan-2-amine (0.70 ml, 4.0 mmol), DMF (0.5 ml) and more dichlormethane (5 ml) were added. Finally, HATU (1.004 g, 2.641 mmol) was added, and the reaction was stirred under nitrogen at room temperature. After stirring for 2.5 weeks, the reaction was filtered and the solid was washed with DCM and MeOH. The filtrate was concentrated and purified on silica gel (˜3 inches, dichlormethane, MeOH, 2 N ammonia in MeOH) to give the desired N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-1-methyl-3-oxo-2-phenyl-5-(pyrrolidin-1-ylmethyl)-2,3-dihydro-1H-pyrazole-4-carboxamide (90.6 mg, 0.165 mmol, 8%). MS (ESI pos. ion) m/z: 551 (MH+). Calc'd exact mass for C31H30N6O4: 550. 1H NMR (400 MHz, CDCl3): 11.44 (s, 1H), 8.61 (d, J=6.0 Hz, 1H), 8.38 (d, J=9.2 Hz, 1H), 8.30-8.21 (m, 2H), 7.62-7.37 (m, 7H), 7.24 (d, J=8.0 Hz, 1H), 6.43 (d, J=6.4 Hz, 1H), 4.35 (s, 2H), 3.98 (s, 3H), 3.57 (s, 3H), 2.73 (s, 4H), 1.84 (s, 4H).

후처리

  1. stirringAfter stirring for 2.5 weeks
  2. filtrationthe reaction was filtered
  3. washthe solid was washed with DCM and MeOH
  4. concentrationThe filtrate was concentrated
  5. custompurified on silica gel (˜3 inches, dichlormethane, MeOH, 2 N ammonia in MeOH)

출처 및 근거

ORD 기록
ord-5ee667a528ee42be8c19de0dd8dd4f3c
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685983B2

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