Morpholine → HCID 68183333, compound

HRID 1615580Notes

Reaction equation

Br[C:2]1[S:23][C:5]2[C:6](=[O:22])[NH:7][C:8]([C:18]([O:20][CH3:21])=[O:19])=[C:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=3)[C:4]=2[CH:3]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:17][C:12]1[CH:11]=[C:10]([C:9]2[C:4]3[CH:3]=[C:2]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[S:23][C:5]=3[C:6](=[O:22])[NH:7][C:8]=2[C:18]([O:20][CH3:21])=[O:19])[CH:15]=[CH:14][C:13]=1[Cl:16]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of methyl 2-bromo-4-(3,4-dichlorophenyl)-7-oxo-6,7-dihydrothieno[2,3-c]pyridine-5-carboxylate (0.081 g, 0.19 mmol), morpholine (0.0489 g, 0.561 mmol), tris(dibenzylideneacetone)dipalladium(0) (17.1 mg, 0.0187 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (21.6 mg, 0.0374 mmol) and cesium carbonate (183 mg, 0.561 mmol) in 1,4-dioxane (3.0 mL, 38 mmol) was heated to 140° C. for 20 min, and then to 150° C. for another 90 min by microwave irradiation. The mixture was concentrated and purified by chromatography and then preparative HPLC to afford the product as a white solid (5.3 mg, 6.4%). LCMS (FA) ES+: 439.4, 441.4. 1H NMR (400 MHz, DMSO) δ 11.30 (s, 1H), 7.67 (d, J=8.3 Hz, 1H), 7.54 (d, J=1.9 Hz, 1H), 7.25 (dd, J=8.2, 2.0 Hz, 1H), 5.76 (s, 1H), 4.09 (d, J=5.1 Hz, 2H), 3.76-3.63 (m, 4H), 3.59 (s, 3H), 3.23-3.06 (m, 4H).

Workup

customto 150° C. for another 90 min by microwave irradiation
concentrationThe mixture was concentrated
custompurified by chromatography

Sources & evidence

ORD record: ord-b8791fb384064fa9b1e2d153301b2e55
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765746B2

Reaction notes

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