Acetic Acid → 8-[(1-acetylpiperidin-4-yl)amino]-N-(2,6-diethylphenyl)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

HRID 81953Notes

Reaction equation

HRID 81953 reaction equation
Cl.[CH2:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][CH3:11])[C:5]=1[NH:12][C:13]([C:15]1[C:19]2[CH2:20][CH2:21][C:22]3[CH:23]=[N:24][C:25]([NH:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[N:26][C:27]=3[C:18]=2[N:17]([CH3:35])[N:16]=1)=[O:14])[CH3:3].CCN(C(C)C)C(C)C.ON1C2C=CC=CC=2N=N1.[C:55](O)(=[O:57])[CH3:56]>CN(C)C=O.O>[C:55]([N:32]1[CH2:31][CH2:30][CH:29]([NH:28][C:25]2[N:24]=[CH:23][C:22]3[CH2:21][CH2:20][C:19]4[C:15]([C:13]([NH:12][C:5]5[C:4]([CH2:2][CH3:3])=[CH:9][CH:8]=[CH:7][C:6]=5[CH2:10][CH3:11])=[O:14])=[N:16][N:17]([CH3:35])[C:18]=4[C:27]=3[N:26]=2)[CH2:34][CH2:33]1)(=[O:57])[CH3:56]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 44555920N-(2,6-diethylphenyl)-1-methyl-8-(piperidin-4-ylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride

Product 1

HCID 445559698-[(1-acetylpiperidin-4-yl)amino]-N-(2,6-diethylphenyl)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamideYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(2,6-diethylphenyl)-1-methyl-8-(piperidin-4-ylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride (40 mg, 0.075 mmol) in dimethylformamide (1 mL), DIPEA (0.2 mL, 1.1 mmol), N-ethyl-N′,N′-diisopropyl carbodiimide hydrochloride (EDCI) (22 mg, 0.113 mmol), 1-hydroxy-benzotriazole (18 mg, 0.113 mmol) and acetic acid (0.005 mL, 0.009 mmol) were added. The mixture was stirred at room temperature for 6 h. Water was added and the mixture extracted with ethylacetate. The organic layer was washed with brine then dried over Na2SO4 and the solvent evaporated to dryness. The crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol: 97/3) to 29 mg of the title compound. (77% yield)

Workup

  1. extractionthe mixture extracted with ethylacetate
  2. washThe organic layer was washed with brine
  3. dry with materialthen dried over Na2SO4
  4. customthe solvent evaporated to dryness
  5. customThe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol: 97/3) to 29 mg of the title compound

Sources & evidence

ORD record
ord-d05b63ba905e4fbd9ac1a9de6257d37b
Source dataset
uspto-grants-2014_09
Patent number
US08846701B2

Reaction notes

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