Ammonia → (5-aminopyridin-3-yl)[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone

HRID 1753040Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[NH3:31]>CN1C(=O)CCC1>[NH2:31][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone (Preparation 43, 643 mg, 1.32 mmol) in NMP (1 mL) was added Cu2O (18.9 mg, 0.132 mmol) and 880 ammonia (6 mL) and the reaction heated to 80° C. in a Reactivial™ for 18 hours followed by an additional 18 hours at 90° C. The reaction was cooled and partitioned between water (15 mL) and EtOAc (20 mL). The aqueous layer was extracted twice with EtOAc (2×20 mL), the organic layers combined, dried and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 50:50 DCM:EtOAc to 80:20 EtOAc:MeOH to afford the title compound as a yellow gum (320 mg, 57%).

Workup

temperatureThe reaction was cooled
custompartitioned between water (15 mL) and EtOAc (20 mL)
extractionThe aqueous layer was extracted twice with EtOAc (2×20 mL)
customdried
concentrationconcentrated in vacuo
customThe residue was purified
washeluting with 50:50 DCM

Sources & evidence

ORD record: ord-875d17ecb0f147fe9e3fc74965122df9
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163021B2

Reaction notes

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