Hydrochloric Acid → 6-Amino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-7-(2,2,2-trifluoroethyl)-7,9-dihydro-8H-purin-8-one

HRID 510096Notes

Reaction equation

[NH2:1][C:2]1[C:7]([N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:9](=[O:12])OC)=[C:6]([NH2:18])[N:5]=[C:4]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([F:28])[CH:26]=3)[N:21]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[F:36])[N:20]=2)[N:3]=1.Cl>O1CCCC1>[NH2:18][C:6]1[N:5]=[C:4]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([F:28])[CH:26]=3)[N:21]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[F:36])[N:20]=2)[N:3]=[C:2]2[C:7]=1[N:8]([CH2:13][C:14]([F:16])([F:17])[F:15])[C:9](=[O:12])[NH:1]2

Participants

Conditions

Temperature: 0 °C

Procedure

Under an argon atmosphere, 5.005 g (6.458 mmol) of the compound from example 32A were dissolved in 355 ml of tetrahydrofuran and cooled to 0° C., and 16.145 ml (16.145 mmol) of a 1N solution of bis(trimethylsilyl)sodium amide in tetrahydrofuran were added dropwise. The mixture was stirred at 0° C. for 2 h and then at RT for 16 h. 16.145 ml (16.145 mmol) of 1N hydrochloric acid were added and the mixture was concentrated on a rotary evaporator. The residue was taken up in ethyl acetate and the organic phase was washed twice with water, dried over sodium sulfate and concentrated on a rotary evaporator. 6.13 g of the title compound were obtained (purity by HPLC 61%). 500 mg of residue were purified by means of preparative HPLC (eluent: methanol/water, gradient 30:70→90:10). 93 mg of the title compound were obtained (36% of theory).

Workup

waitat RT for 16 h
concentrationthe mixture was concentrated on a rotary evaporator
washthe organic phase was washed twice with water
dry with materialdried over sodium sulfate
concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record: ord-b9a4190486394b2a80d82f343f71642f
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096592B2

Reaction notes

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