Sodium Chloride → 5,7-dihydro-6H-pyrazolo[3,4-h]quinazoline-9-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide

HRID 23436

Reaction equation

[CH2:1]([N:3]([CH2:27][CH3:28])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[N:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[C:25]3[C:24](=O)[CH2:23][CH2:22][CH2:21][C:20]=3[NH:19][N:18]=2)=[O:16])=[CH:10][CH:9]=1)[CH3:2].[CH3:29][N:30]([CH:32](N(C)C)[N:33](C)C)C.C(O)(=O)C.C(N)=N.[Na+].[Cl-].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[CH2:1]([N:3]([CH2:27][CH3:28])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[N:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[C:25]3[C:24]4[N:33]=[CH:32][N:30]=[CH:29][C:23]=4[CH2:22][CH2:21][C:20]=3[NH:19][N:18]=2)=[O:16])=[CH:10][CH:9]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide (192 mg, 0.50 mmol) and tris(dimethylamino)methane (181 mg, 1.25 mmol) is stirred in a pressure reactor at 60° C. for 5 hours. After cooling, the reaction mixture is dissolved in ethanol (5 mL), treated with formamidine acetate (1.00 g, 9.6 mmol), and stirred in a pressure reactor at 110° C. for 18 hours. The reaction mixture is poured into 10% NaCl (50 mL), treated with 1 M sodium carbonate to pH 11 and extracted with chloroform (40 mL). The extract is dried over sodium carbonate, and the solvent is evaporated under reduced pressure. The residue is triturated with diethyl ether to give pure crystalline 5,7-dihydro-6H-pyrazolo[3,4-h]quinazoline-9-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide. 1H NMR (CD3OD) t, J=7.1 Hz, 6H), 1.98 (m, 2H), 2.61 (q, J=7.1 Hz, 4H), 2.69 (m, 2H), 3.10 (m, 2H), 3.16 (m, 2H), 4.32 (t, J=6.2 Hz, 2H), 6.84 (dd, J=8.8 and 0.5 Hz, 1H), 8.17 (dd, J=8.9 and 2.7 Hz, 1H), 8.51 (dd, J=2.7 and 0.5 Hz, 1H), 8.65 (s, 1H), 9.09 (s, 1H) MW 421.507; MS (M+H)+ 422.

Workup

temperatureAfter cooling
stirringstirred in a pressure reactor at 110° C. for 18 hours
extractionextracted with chloroform (40 mL)
dry with materialThe extract is dried over sodium carbonate
customthe solvent is evaporated under reduced pressure
customThe residue is triturated with diethyl ether

Sources & evidence

ORD record: ord-dbf56c7edf0848a7b67cd8132edc22b4
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06852730B2

Linked notes

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