Cesium carbonate → 5-(1H-pyrrolo[2,3-c]pyridin-5-ylamino)pyrazine-2-carbonitrile

HRID 40693Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8](C(OC(C)(C)C)=O)[C:5]2=[CH:6][N:7]=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:25]#[N:26])=[N:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[NH:8]1[C:5]2=[CH:6][N:7]=[C:2]([NH:18][C:19]3[N:20]=[CH:21][C:22]([C:25]#[N:26])=[N:23][CH:24]=3)[CH:3]=[C:4]2[CH:10]=[CH:9]1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of tert-butyl 5-chloro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (0.030 g, 0.119 mmol), 5-aminopyrazine-2-carbonitrile (0.017 g, 0.142 mmol), cesium carbonate (0.077 g, 0.237 mmol), Xantphos (0.011 g, 0.019 mmol) and tris(benzylideneacetone)dipalladium (0) (0.009 g, 0.010 mmol) in dioxane (0.8 mL) was degassed by bubbling argon through the mixture for 10 minutes. The sealed reaction vessel was heated to 150° C. for 1 hour in a microwave reactor. The crude mixture was filtered through an SCX-2 acidic resin cartridge, eluting with 2 M ammonia in methanol. The basic filtrate was concentrated and purified by column chromatography to give the title compound (0.018 g, 0.054 mmol, 45%). LC-MS (3) Rt=1.30 min; m/z (ESI+) 237 (M+H).

Workup

customwas degassed
customby bubbling argon through the mixture for 10 minutes
customThe sealed reaction vessel
filtrationThe crude mixture was filtered through an SCX-2 acidic resin cartridge
washeluting with 2 M ammonia in methanol
concentrationThe basic filtrate was concentrated
custompurified by column chromatography

Sources & evidence

ORD record: ord-58171aae7fd94b37a68ecf7ba112ffeb
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530468B2

Reaction notes

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