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 2359671Notes

Reaction equation

HRID 2359671 reaction equation
[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

Participants

7

Reactant 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

Product 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-carboxamideYield 8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-5ee667a528ee42be8c19de0dd8dd4f3c
Source dataset
uspto-grants-2014_04
Patent number
US08685983B2

Reaction notes

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