6-Chloro-3-pyridinecarbonitrile → 6-((1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)nicotinonitrile

HRID 2204501Notes

Reaction equation

Cl.[C:2]1([C@@H:14]2[CH2:18][CH2:17][C@H:16]([NH2:19])[CH2:15]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1.Cl[C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=1>CCO>[C:2]1([C@@H:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C:21]3[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=3)[CH2:15]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a microwave vessel was added (1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride (0.0979 g, 0.311 mmol, Example #6, Step C), EtOH (2 mL), 6-chloronicotinonitrile (0.057 g, 0.41 mmol), and TEA (0.130 mL, 0.932 mmol). The reaction mixture was heated in a CEM™ microwave at about 130° C. for about 1 h (250 psi maximum pressure, 5 min maximum ramp, 300 maximum watts). After cooling to ambient temperature, the reaction was concentrated under reduced pressure and purified by silica gel chromatography eluting with DCM/MeOH/Et2NH (970:27:3) to give 6-((1S,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)nicotinonitrile (0.027 g, 25%): LC/MS (Table 2, Method a) Rt=1.24 min; MS m/z: 345(M+H)+.

Workup

temperatureAfter cooling to ambient temperature
concentrationthe reaction was concentrated under reduced pressure
custompurified by silica gel chromatography
washeluting with DCM/MeOH/Et2NH (970:27:3)

Sources & evidence

ORD record: ord-f5a7996fc8494eeab1d7fb1fb0d9867f
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365579B2

Reaction notes

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