Pyridine → 1-(4-(2-(6-(1,3-Dioxan-2-yl)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea

HRID 1400899Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1.[N:31]1[CH:36]=C[CH:34]=[CH:33][CH:32]=1.ClC(OC1C=CC=CC=1)=[O:39].C1(N)CC1>CN(C=O)C.O>[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH:27][C:36]([NH:31][CH:32]4[CH2:34][CH2:33]4)=[O:39])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of compound 280 (6.32 g, 14.92 mmol) and pyridine (2.41 mL, 17.91 mmol) in DMF (70 mL) at 0° C. was added phenyl chloroformate (2.25 mL, 17.91 mmol). After 30 min cyclopropylamine (2.63 mL, 37.3 mmol) was added at RT and the reaction mixture was heated at 60° C. for 45 min. After cooling to RT the reaction mixture was diluted with water to form a precipitate that was collected by filtration, dried and purified by Biotage (SNAP 100 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV), to produce a material that upon trituration with EtOAc afforded the title compound 281 (2.71 g, 5.35 mmol, 36% yield) as a beige solid. MS (m/z): 507.2 (M+H).

Workup

temperatureAfter cooling to RT the reaction mixture
customto form a precipitate that
filtrationwas collected by filtration
customdried
custompurified by Biotage (SNAP 100 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV)
customto produce a material that upon trituration with EtOAc

Sources & evidence

ORD record: ord-76f579626abb467fabaa949f7d9f7e9e
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906852B2

Reaction notes

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