Ammonia → (5-Aminopyridin-3-yl){7-[(1R)-1-methyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}methanone

HRID 82154

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([C@H:19]([CH3:28])[CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[NH3:29].C(OCC)(=O)C.O>CN1CCCC1=O.[Cu-]=O>[NH2:29][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([C@H:19]([CH3:28])[CH2:20][O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Copper (I) oxide (9.2 mg, 0.06 mmol) was added to (5-bromopyridin-3-yl){7-[(1R)-1-methyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}methanone (285 mg, 0.64 mmol) (see Preparation 26) and concentrated ammonia solution (2 mL) in 1-methyl-2-pyrrolidinone (0.5 mL). The mixture was heated in a sealed vessel at 80° C. for 17 hours. Ethyl acetate (5 mL) and water (5 mL) were added to the reaction mixture and then filtered through a glass fibre filter. The organic phase was dried over magnesium sulfate and evaporated in vacuo. The crude solid was purified by column chromatography on silica gel (gradient of EtOAc:MeOH:cNH3 100:0:0 to 95:5:0.5) to afford the title compound as a colourless oil in 70% yield, 171 mg.

Workup

filtrationfiltered through a glass fibre filter
dry with materialThe organic phase was dried over magnesium sulfate
customevaporated in vacuo
customThe crude solid was purified by column chromatography on silica gel (gradient of EtOAc:MeOH:cNH3 100:0:0 to 95:5:0.5)

Sources & evidence

ORD record: ord-d3b068f05cf64f64a4cd928e4028c651
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846698B2

Linked notes

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