Acetic Acid → HCID 68154087, compound

HRID 341092Notes

Reaction equation

HRID 341092 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[C:32](=[O:33])[C:11]2=[CH:12][N:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)=[CH:23][CH:22]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]2=[N:9]1.C(O)(=O)C.[CH3:38][NH2:39].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.O.CO>[CH3:38][NH:39][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[N:8]1[C:32](=[O:33])[C:11]2=[CH:12][N:13]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([N:27]4[CH:31]=[CH:30][CH:29]=[N:28]4)=[CH:25][CH:26]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]2=[N:9]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 68153779HCID 68153779, compound

Product 1

HCID 68154087HCID 68154087, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

(±)-2-(2-Oxocyclohexyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 720, 45 mg, 0.10 mmol) was dissolved in 1,2-dichloroethane (3 mL) and treated with acetic acid (0.029 mL, 0.51 mmol, 5 equiv) and methylamine (0.057 mL, 0.11 mmol, 1.1 equiv). After stirring for 20 minutes at ambient temperature, sodium triacetoxyborohydride (30 mg, 0.14 mmol, 1.4 equiv) was added and the mixture was vigorously stirred for 4 hours. The mixture was treated with methanol (1 mL), poured into water (15 mL) and extracted once with ethyl acetate (20 mL). The organic layer was discarded and the aqueous layer was treated with sodium bicarbonate (15 mL, aqueous saturated) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.45 (1H, s), 8.41-8.38 (1H, m), 7.89 (1H, d, J=2.5 Hz), 7.71 (1H, d, J=1.6 Hz), 7.70 (2H, d, J=8.5 Hz), 7.49-7.43 (2H, m), 7.41-7.38 (1H, m), 7.27 (2H, d, J=8.5 Hz), 6.47-6.46 (1H, m), 5.50 (1H, d, J=16.5 Hz), 5.44 (1H, d, J=16.5 Hz), 4.75 (1H, dt, J=10.5, 3.8 Hz), 3.02 (1H, m), 2.49-2.33 (1H, m), 2.37 (3H, s), 2.14-2.09 (1H, m), 1.98-1.92 (1H, m), 1.87-1.80 (1H, m), 1.70-1.59 (2H, m), 1.57-1.42 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 453.2387 [(M+H)+; calculated for C27H29N6O: 453.2397].

Workup

  1. stirringthe mixture was vigorously stirred for 4 hours
  2. extractionextracted once with ethyl acetate (20 mL)
  3. additionthe aqueous layer was treated with sodium bicarbonate (15 mL, aqueous saturated)
  4. extractionextracted with ethyl acetate (2×30 mL)
  5. dry with materialThe combined organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-899038805b874b62a93f626fa8476ad4
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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