Dimethylformamide → [2-Chloro-4-(3-methyl-1H-pyrazol-1-yl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone

HRID 636367Notes

Reaction equation

HRID 636367 reaction equation
[N:1]1[C:6]2[NH:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[NH:10][CH2:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:22][C:23]1[CH:31]=[C:30](F)[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26].C[N:34]([CH3:37])C=O>O>[Cl:22][C:23]1[CH:31]=[C:30]([N:34]2[CH:37]=[CH:9][C:8]([CH3:15])=[N:7]2)[CH:29]=[CH:28][C:24]=1[C:25]([N:10]1[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[NH:7][C:6]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:11]1)=[O:26]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 11430Potassium CarbonateHCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 110307606,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Product 1

HCID 9888109[2-Chloro-4-(3-methyl-1H-pyrazol-1-yl)-phenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanoneYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Step B (12.8 g, 65 mmol) in dimethylformamide (120 mL) under nitrogen was added potassium carbonate (19.76 g, 143 mmol). The mixture was cooled and treated dropwise with a solution of crude 2-chloro-4-fluorobenzoyl chloride of Step C (78 mmol) in dimethylformamide (50 mL). After stirring at room temperature for 75 minutes the mixture was diluted with water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate and evaporated to dryness. The crude material was purified by flash chromatography (on silica Merck-60, hexane-ethyl acetate gradient from 95:5 to 80:20) to provide the pure title compound (14.25 g, 62%) along with some less pure material (2.7 g). The pure material is an off-white crystalline solid, which is used as such in the next step.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. customevaporated to dryness
  5. customThe crude material was purified by flash chromatography (on silica Merck-60, hexane-ethyl acetate gradient from 95:5 to 80:20)

Sources & evidence

ORD record
ord-341b67f6e1f8443e84678bc86a02817a
Source dataset
uspto-grants-2001_02
Patent number
US06194407B1

Reaction notes

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