Morpholine → N-(4-(2,6-dichlorobenzamido)pyridin-2-yl)-2-morpholinothiazole-5-carboxamide

HRID 449868Notes

Reaction equation

Br[C:2]1[S:3][C:4]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([NH:16][C:17](=[O:26])[C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])[CH:13]=[CH:12][N:11]=2)=[O:8])=[CH:5][N:6]=1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>C(O)CCC>[Cl:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]([Cl:24])[C:18]=1[C:17]([NH:16][C:14]1[CH:13]=[CH:12][N:11]=[C:10]([NH:9][C:7]([C:4]2[S:3][C:2]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[N:6][CH:5]=2)=[O:8])[CH:15]=1)=[O:26]

Participants

Conditions

Temperature: 50 °C

Procedure

To a suspension of 2-bromo-N-(4-(2,6-dichlorobenzamido)pyridin-2-yl)thiazole-5-carboxamide (Example 7) (24.0 mg, 0.051 mmol) in 1-butanol (1 mL) was added morpholine (44.4 mg, 0.51 mmol). The mixture was heated at 50° C. for 6 hours. The mixture was then concentrated under reduced pressure, and the residue was purified by reverse-phase HPLC (Gemini, 3×10 cm, gradient: 5-85% CH3CN/H2O with 0.1% NH4OH over 10 min) to afford the desired product (17 mg, 69.4% yield). 1H NMR (400 MHz, DMSO) δ 11.18 (s, 1H), 10.68 (s, 1H), 8.38 (s, 1H), 8.32 (s, 1H), 8.27 (d, J=5.5, 1H), 7.63-7.57 (m, 2H), 7.56-7.51 (m, 2H), 3.73-3.68 (m, 4H), 3.52-3.46 (m, 4H). LCMS (ESI) m/z: 478.2 [M+H+]

Workup

concentrationThe mixture was then concentrated under reduced pressure
customthe residue was purified by reverse-phase HPLC (Gemini, 3×10 cm, gradient: 5-85% CH3CN/H2O with 0.1% NH4OH over 10 min)

Sources & evidence

ORD record: ord-a322d0aaa2af48ecb8f95190d7e3dbbe
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486950B2

Reaction notes

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