Diisopropylethylamine → 6-Amino-4-(bicyclo[1.1.1]pentan-1-ylamino)nicotinonitrile

HRID 1778031Notes

Reaction equation

[C:1]12([NH2:6])[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.[NH2:7][C:8]1[CH:15]=[C:14](F)[C:11]([C:12]#[N:13])=[CH:10][N:9]=1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[NH2:7][C:8]1[CH:15]=[C:14]([NH:6][C:1]23[CH2:5][CH:3]([CH2:4]2)[CH2:2]3)[C:11]([C:12]#[N:13])=[CH:10][N:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of bicyclo[1.1.1]pentan-1-ylamine (201 mg, 1.68 mmol), 6-amino-4-fluoronicotinonitrile (intermediate 21, 230 mg, 1.68 mmol) and diisopropylethylamine (1.47 ml, 8.39 mmol) in DMA (3 ml) was heated at 80° C. in a septum sealed reaction vessel for 48 h. The reaction mixture was heated for 5 h at 120° C. and 18 h at 80° C., then cooled, evaporated and purified twice by normal phase chromatography using 24 g RediSep® columns, eluting with gradients from heptane to EtOAc. Product containing fractions were combined and evaporated to give the title compound.

Workup

customsealed
customreaction vessel for 48 h
temperatureThe reaction mixture was heated for 5 h at 120° C. and 18 h at 80° C.
temperaturecooled
customevaporated
custompurified twice by normal phase chromatography
washeluting with gradients from heptane to EtOAc
additionProduct containing fractions
customevaporated

Sources & evidence

ORD record: ord-31eca8b829954827b766cf9628d463ae
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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