Acetic Acid → HCID 68154602, compound

HRID 341069Notes

Reaction equation

HRID 341069 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:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH:29]=O.[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(Cl)(Cl)Cl>[N:22]1([C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=4[C:5]4=[N:4][N:3]([C:27]5[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=5[CH2:29][N:35]5[CH2:39][CH2:38][CH2:37][CH2:36]5)[C:2](=[O:1])[C:6]4=[CH:7]3)=[CH:17][CH:18]=2)[CH:26]=[CH:25][CH:24]=[N:23]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86668679HCID 86668679, compound

Product 1

HCID 68154602HCID 68154602, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

2-(3-Oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)benzaldehyde (Example 529, 0.15 g, 035 mmol) and pyrrolidine (0.031 mL, 0.38 mmol, 1.1 equiv) were combined in 1,2-dichloroethane (2 mL) and treated with powdered 4 Å molecular sieves (0.15 g, 1 wt equiv) and acetic acid (0.099 mL, 1.7 mmol, 5 equiv). After stirring vigorously for 20 minutes at ambient temperature, the mixture was treated with sodium triacetoxyborohydride (0.11 g, 0.52 mmol, 1.5 equiv) portionwise over 2 minutes. After stirring for 90 minutes, the mixture was treated with sodium bicarbonate (7 mL, aqueous saturated) and stirred for 5 minutes. The mixture was diluted with chloroform (20 mL), filtered and the organic filtrate was washed once with sodium bicarbonate (10 mL, aqueous saturated) and brine (10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 90:10; chloroform:methanol; then 92:8; chloroform:methanol containing 10% ammonium hydroxide), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.12 (1H, br s), 8.46 (1H, dd, J=2.5, 0.4 Hz), 8.32 (1H, s), 8.20 (1H, d, J=8.1 Hz), 7.84 (2H, d, J=8.8 Hz), 7.78 (1H, d, J=8.3 Hz), 7.73 (1H, d, J=1.7 Hz). 7.65-7.60 (2H, m), 7.53 (1H, t, J=7.4 Hz), 7.48 (2H, d, J=8.6 Hz), 7.45-7.33 (2H, m), 6.53 (1H, dd, J=2.5, 1.8 Hz), 5.77 (2H, s), 3.63 (2H, br m), 2.36 (4H, br m), 1.63 (4H, br m) ppm; low resolution mass spectrometry (ES+) m/z 501.0 [(M+H)+; calculated for C31H29N6O: 501.2].

Workup

  1. stirringAfter stirring for 90 minutes
  2. stirringstirred for 5 minutes
  3. filtrationfiltered
  4. washthe organic filtrate was washed once with sodium bicarbonate (10 mL, aqueous saturated) and brine (10 mL)
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel gradient chromatography (100:0 to 90:10

Sources & evidence

ORD record
ord-714297d233c94e8a8d1c1c873328d560
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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