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

HRID 222271Notes

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 sulfate, 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 sulfate
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by column chromatography (0-40% ethyl acetate/hexane gradient)

Sources & evidence

ORD record: ord-053d957fb3614c488fcc211c54fab313
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207186B2

Reaction notes

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