Methylamine → HCID 52913021, compound

HRID 341065Notes

Reaction equation

HRID 341065 reaction equation
[O:1]=[C:2]1[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:18][CH:17]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4][N:3]1[C:27]1[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=1[C:29](O)=[O:30].F[P-](F)(F)(F)(F)F.[N:43]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:47]2C=CC=CC=2N=N1.CN.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:47][NH:43][C:29](=[O:30])[C:28]1[CH:32]=[CH:33][CH:34]=[CH:35][C:27]=1[N:3]1[C:2](=[O:1])[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:18][CH:17]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4]1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 52913020HCID 52913020, compound

Product 1

HCID 52913021HCID 52913021, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3-Oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)benzoic acid (Example 611, 41 mg, 0.089 mmol) was suspended in dichloromethane (3 mL), treated with (1H-1,2,3-benzotriazol-1-yloxy) (tripyrrolidin-1-yl)phosphonium hexafluorophosphate (PyBOP, 69 mg, 0.13 mmol, 1.5 equiv) and methylamine (1.0 mL, 2 M tetrahydrofuran solution, 2.0 mmol, 22 equiv). After stirring for 1 hour, the mixture was poured into sodium bicarbonate (20 mL, aqueous saturated) and extracted with chloroform (3×25 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.11 (1H, s), 8.45 (1H, d, J=2.5 Hz), 8.16 (1H, dd, J=7.9, 1.5 Hz), 8.11 (1H, q, J=5.0 Hz), 7.83 (2H, d, J=8.6 Hz), 7.76 (1H, d, J=8.5 Hz), 7.72 (1H, d, J=1.5 Hz), 7.70 (1H, d, J=7.9 Hz), 7.61 (1H, ddd, J=8.3, 7.3, 1.8 Hz), 7.56-7.52 (2H, m), 7.49 (1H, dd, J=7.7, 1.5 Hz), 7.46 (2H, d, J=8.9 Hz), 7.36 (1H, td, J=7.5, 1.1 Hz), 6.53 (1H, dd, J=2.4, 1.8 Hz), 5.76 (2H, s), 2.66 (3H, d, J=4.6 Hz) ppm; high resolution mass spectrometry (ES+) m/z 475.1896 [(M+H)+; calculated for C28H23N6O2: 475.1877].

Workup

  1. extractionextracted with chloroform (3×25 mL)
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-367f9559bbc146378d3dd9e621c5b951
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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