Potassium Carbonate → 1-(4-{4-[2-chloro-7-(methylamino)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone

HRID 389461Notes

Reaction equation

[Cl:1][C:2]1[O:13][C:5]2=[C:6]([NH:11][CH3:12])[N:7]=[CH:8][C:9](I)=[C:4]2[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33](=[O:35])[CH3:34])[CH2:29][CH2:28]3)[CH:26]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[Cl:1][C:2]1[O:13][C:5]2=[C:6]([NH:11][CH3:12])[N:7]=[CH:8][C:9]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:28][CH2:29][N:30]([C:33](=[O:35])[CH3:34])[CH2:31][CH2:32]4)[CH:26]=3)=[C:4]2[CH:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 2-chloro-4-iodo-N-methylfuro[2,3-c]pyridin-7-amine (125 mg, 0.405 mmol), 1-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (142 mg, 0.446 mmol), (1,1′-bis-(diphenylphosphine)-ferrocene)palladium dichloride (29.6 mg, 0.0405 mmol) and potassium carbonate (140 mg, 1.01 mmol) in 1,4-dioxane (1.35 mL) and water (0.58 mL) was heated to 95° C. for 20 h. The mixture was adsorbed directly onto a dry 5 g silica gel cartridge and purified by ISCO chromatography (0 to 10% methanol:ethyl acetate) to afford 150 mg (99%) of the title compound as a tan solid. 1H NMR (400 MHz, CD3OD): δ 8.06 (s, 1 H), 7.92 (s, 1 H), 7.82 (s, 1 H), 7.05 (s, 1 H), 4.74-4.60 (m, 1 H), 4.51 (tt, J=4.4, 11.5 Hz, 1 H), 4.14-4.00 (m, 1 H), 3.39-3.34 (m, 1 H), 3.05 (s, 3 H), 2.85 (td, J=3.0, 13.0 Hz, 1 H), 2.28-2.11 (m, 5 H), 2.11-1.89 (m, 2 H); MS (ESI): 374.11, 376.08 [M+H]+; HPLC tR=2.29 min (ZQ3, polar—4 min).

Workup

custompurified by ISCO chromatography (0 to 10% methanol:ethyl acetate)

Sources & evidence

ORD record: ord-7684a083ade44b07ab667d967674e2f1
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378104B2

Reaction notes

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