Tetrahydrofuran → 1-(1-(1H-imidazole-1-carbonyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

HRID 1184957Notes

Reaction equation

[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].C(N(C(C)C)CC)(C)C.O1CCCC1.Cl.Cl.N1CC[CH:32]([N:35]2[C:43]3[C:38](=[N:39][CH:40]=[CH:41][CH:42]=3)[NH:37][C:36]2=[O:44])[CH2:31]C1>C(#N)C>[N:8]1([C:1]([N:3]2[CH2:4][CH2:31][CH:32]([N:35]3[C:43]4[C:38](=[N:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]3=[O:44])[CH2:6][CH2:7]2)=[O:2])[CH:12]=[CH:11][N:10]=[CH:9]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a round bottom flask was added, 1,1′-carbonyldiimidazole (8.59 g, 51.4 mmol), diisopropylethylamine (12.6 mL, 72.2 mmol) and tetrahydrofuran (100 mL). This mixture was warmed to 40° C. and aged for 10 min, after which 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one dihydrochloride (10 g, 34.3 mmol) was added. The slurry was aged at 40° C. for 3 h, and then upon reaction completion, the solvent was swapped to acetonitrile which afforded an off white solid (9.19 g, 85.9%). LCMS: [M+H]=313; 1H NMR (400 MHz, d6-DMSO) δ 11.58 (1H, s), 8.09 (1H, s), 7.97 (1H, d, J=8.0 Hz), 7.73 (1H, d, J=4.0 Hz), 7.53 (1H, s), 7.05 (1H, s), 7.00 (1H, dd, J=4.0, 8.0 Hz), 4.52, (1H, dd, J=8.0, 12.0 Hz), 4.05 (2H, bd, J=8.0 Hz), 3.31 (2H, m), 2.34 (2H, m), 1.82 (2H, bd, J=12.0 Hz); 13C NMR (100 MHz, d6-DMSO) δ 153.0, 150.4, 143.4, 139.8, 137.2, 128.9, 123.0, 118.7, 116.4, 115.2, 49.3, 45.1, 28.5; mp 226° C.

Workup

additionTo a round bottom flask was added
customupon reaction completion

Sources & evidence

ORD record: ord-6343dfc42ccd4b64af5a38e40fad80c6
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669368B2

Reaction notes

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