Ammonium Hydroxide → (5-Amino-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone

HRID 82278Notes

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:19]3([CH2:22][O:23][CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[CH2:21][CH2:20]3)[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[OH-].[NH4+:31]>CN1CCCC1=O.[Cu-]=O>[NH2:31][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:19]3([CH2:22][O:23][CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[CH2:21][CH2:20]3)[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a stirred solution of (5-Bromo-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone (Preparation 250, 200 mg, 0.45 mmol) in 1-Methyl-pyrrolidin-2-one (1.5 mL) was added ammonium hydroxide (15 mL). Then copper (I) oxide (3 mg, 0.02 mmol) was added and the reaction mixture was heated in a sealed tube at 130° C. for 16 hours. The reaction mixture was cooled to room temperature, extracted with 10% methanol in dichloromethane (5×25 mL). The combined organic layer was dried over sodium sulphate and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of dichloromethane:methanol 100:0 to 96:4) to afford the title compound as a white sticky solid in 45% yield, 80 mg.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with 10% methanol in dichloromethane (5×25 mL)
dry with materialThe combined organic layer was dried over sodium sulphate
customevaporated in vacuo
customThe crude material was purified by column chromatography on silica gel (gradient of dichloromethane:methanol 100:0 to 96:4)

Sources & evidence

ORD record: ord-ed2cfc1286b74c8f8555a8f211cac345
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846698B2

Reaction notes

Loading…