proline dl-form → 3-chloro-7-{[(3-methylpyridin-2-yl)methyl]amino}-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

HRID 1987097Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:16]=[CH:15][C:9]3=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=[C:8]3[C:7](=[O:17])[C:6]=2[CH:18]=1.[NH2:19][CH2:20][C:21]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=1.C(=O)([O-])[O-].[K+].[K+].N1CCCC1C(O)=O>[Cu](I)I.CS(C)=O>[Cl:14][C:12]1[CH:13]=[C:8]2[C:7](=[O:17])[C:6]3[CH:18]=[C:2]([NH:19][CH2:20][C:21]4[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=4)[CH:3]=[CH:4][C:5]=3[CH:16]=[CH:15][C:9]2=[N:10][CH:11]=1

Participants

Conditions

Temperature: 70 °C

Procedure

7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (0.100 g, 0.312 mmol), 2-aminomethyl-3-methylpyridine (0.038 g, 0.312 mmol), copper iodide (0.006 g, 0.031 mmol), potassium carbonate (0.086 g, 0.621 mmol), and dl-proline (0.007 g, 0.062 mmol) were combined in a flask. Dimethyl sulfoxide (2.0 mL) was added and argon was bubbled through the solution for several minutes. The solution was stirred and heated at 70° C. overnight. Once complete the solution was cooled to ambient temperature, diluted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulftate, filtered, concentrated in vacuo and purified by column chromatography (0-40% ethyl acetate/hexane gradient) to afford the title compound.

Workup

customargon was bubbled through the solution for several minutes
temperatureOnce complete the solution was cooled to ambient temperature
additiondiluted with ethyl acetate
washwashed with water
dry with materialThe organic layer was dried over magnesium sulftate
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by column chromatography (0-40% ethyl acetate/hexane gradient)

Sources & evidence

ORD record: ord-8c25f2b40444469382ae5e027da9ed6b
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550478B2

Reaction notes

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