Dimethylformamide → HCID 11952517, compound

HRID 548603Notes

Reaction equation

HRID 548603 reaction equation
[CH:1]([N:4]=[C:5]=[O:6])([CH3:3])[CH3:2].Cl.Cl.[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][NH:17][C:18]2[N:19]([CH2:32][CH2:33][CH3:34])[N:20]=[C:21]3[C:30]=2[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N:23]=[C:22]3[NH2:31])[CH2:11][CH2:10]1.C(N(CC)CC)C.CN(C)C=O>ClCCl>[NH2:31][C:22]1[C:21]2=[N:20][N:19]([CH2:32][CH2:33][CH3:34])[C:18]([NH:17][CH2:16][CH2:15][CH:12]3[CH2:13][CH2:14][N:9]([C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:6])[CH2:10][CH2:11]3)=[C:30]2[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[N:23]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 61277Isopropyl isocyanateHCID 86630221HCID 86630221, compound

Product 1

HCID 11952517HCID 11952517, compoundYield 10.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isopropyl isocyanate (0.29 g, 0.33 mL, 3.39 mmol) was added to a stirring suspension of N1-(2-piperidin-4-ylethyl)-2-propyl-2H-pyrazolo[3,4-c]quinoline-1,4-diamine dihydrochloride (1.2 g, 2.83 mmol) and triethylamine (2.9 g, 3.9 mL, 28.3 mmol) in dichloromethane (100 mL). After 10 minutes, N,N-dimethylformamide (15 mL) was added and the resulting suspension was stirred at ambient temperature 16 hours. The dichloromethane was removed under reduced pressure and water (100 mL) was added to the resulting oil. A solid formed which was removed by filtration and discarded. The filtrate was transferred to a separatory funnel and extracted with dichloromethane (50 mL). The aqueous layer was saturated with solid sodium bicarbonate and extracted with dichlioromethane (3×50 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting brown oil was purified by column chromatography using a HORIZON HPFC system (silica cartridge, eluting with 3-15% methanol in dichloromethane). The resulting oil was crystallized from acetonitrile and isolated by filtration to yield 132 mg of 4-{2-[(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)amino]ethyl}-N-isopropylpiperidine-1-carboxamide as a white solid, mp 168-170° C. Anal. calcd for C24H35N7O: C, 65.88; H, 8.06; N, 22.41. Found: C, 65.89; H, 8.24; N, 22.67.

Workup

  1. customThe dichloromethane was removed under reduced pressure and water (100 mL)
  2. additionwas added to the resulting oil
  3. customA solid formed which
  4. customwas removed by filtration
  5. customThe filtrate was transferred to a separatory funnel
  6. extractionextracted with dichloromethane (50 mL)
  7. extractionextracted with dichlioromethane (3×50 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting brown oil was purified by column chromatography
  12. washa HORIZON HPFC system (silica cartridge, eluting with 3-15% methanol in dichloromethane)
  13. customThe resulting oil was crystallized from acetonitrile
  14. customisolated by filtration

Sources & evidence

ORD record
ord-18afef6e86034f89bab068ae42f133dc
Source dataset
uspto-grants-2011_05
Patent number
US07943610B2

Reaction notes

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