Diisopropylethylamine → N-cyclopropyl-3-(1-(3-hydroxy-4,5-dihydro-1H-pyrazolo[3,4-c]pyridin-6(7H)-yl)phthalazin-6-yl)-4-methylbenzamide

HRID 2357682Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:21]=[CH:22][C:23]=3[CH3:24])[C:15]([NH:17][CH:18]3[CH2:20][CH2:19]3)=[O:16])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.[NH:25]1[C:29]2[CH2:30][NH:31][CH2:32][CH2:33][C:28]=2[C:27]([OH:34])=[N:26]1.C(N(CC)C(C)C)(C)C>CN1C(=O)CCC1.O>[CH:18]1([NH:17][C:15](=[O:16])[C:14]2[CH:21]=[CH:22][C:23]([CH3:24])=[C:12]([C:8]3[CH:7]=[C:6]4[C:11](=[CH:10][CH:9]=3)[C:2]([N:31]3[CH2:32][CH2:33][C:28]5[C:27]([OH:34])=[N:26][NH:25][C:29]=5[CH2:30]3)=[N:3][N:4]=[CH:5]4)[CH:13]=2)[CH2:20][CH2:19]1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 3-(1-chlorophthalazin-6-yl)-N-cyclopropyl-4-methylbenzamide (300 mg, 888 μmol), 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-3-ol (247 mg, 1776 μmol) and N,N-diisopropylethylamine (310 μl, 1776 μmol) in NMP (3 mL) was heated to 160° C. for 18 h. After cooling to RT, the mixture was diluted with H2O and extracted with 25% i-PrOH/CHCl3 (3×). The combined organics were dried over Na2SO4, filtered and concentrated. The residue was purified with reverse-phase chromatography (Phenomenex Synergi 4m Max RP 80 A column, 150×21 mM, 20 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10.5 min gradient) to obtain the title compound. MS (ESI, pos. ion) m/z: 441 (M+1).

Workup

temperatureAfter cooling to RT
extractionextracted with 25% i-PrOH/CHCl3 (3×)
dry with materialThe combined organics were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified with reverse-phase chromatography (Phenomenex Synergi 4m Max RP 80 A column, 150×21 mM, 20 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10.5 min gradient)

Sources & evidence

ORD record: ord-cf8c7b295e03456b9646d5136437ffb0
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07759337B2

Reaction notes

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