Hydrochloric Acid → HCID 54675651, compound

HRID 2203370Notes

Reaction equation

[NH2:1][C:2]1[C:3]2[C:29]([CH3:36])([C:30]([NH:32][CH:33]3[CH2:35][CH2:34]3)=[O:31])[C:28](=[O:37])[NH:27][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][C:13](Cl)=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[N:9]=2)[N:7]=1.[CH3:38][O-:39].[Na+].Cl>CO>[NH2:1][C:2]1[C:3]2[C:29]([CH3:36])([C:30]([NH:32][CH:33]3[CH2:35][CH2:34]3)=[O:31])[C:28](=[O:37])[NH:27][C:4]=2[N:5]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][C:13]([O:39][CH3:38])=[CH:14][CH:15]=3)[N:10]([CH2:18][CH2:19][C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[N:9]=2)[N:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A methanol (1.5 mL, anhydrous) solution containing 4-amino-2-(6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-N-cyclopropyl-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-5-carboxamide, as described in Example 176, (62 mg, 0.114 mmol) and sodium methoxide (0.21 ml, 0.91 mmol, 25% in methanol) was stirred for 10 hours at 60° C. The reaction mixture was cooled and adjusted to pH 7.0 with 2N HCl aq. at 0° C. The residue was purified by reverse phase HPLC to afford the indicated product. Chiral separation using SFC on a Chiralcel OJ column provided both enantiomers of the title compound. 1H NMR (500 MHz, CD3COCD3): δ 0.61 (m, 2H); 0.77 (M, 2H); 1.83 (s, 3H); 2.85 (m, 1H); 3.04 (m, 2H); 4.05 (s, 3H); 4.88 (m, 2H); 6.78 (d, J=8.7 Hz, 2H); 7.72 (br, 1H); 7.84 (d, J=8.6 Hz, 1H); 9.13 (d, J=8.6 Hz, 1H). m/z=541.21 (M+H).

Workup

temperatureThe reaction mixture was cooled
customThe residue was purified by reverse phase HPLC
customto afford the indicated product
customChiral separation

Sources & evidence

ORD record: ord-d60cfdebbd814e7884d8357f5d6c9d39
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365574B2

Reaction notes

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