Dimethylformamide → [2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5,11-dihydro-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)-methanone

HRID 636369

Reaction equation

HRID 636369 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+].[Br: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.ClCCl>[Br: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

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 11430Potassium CarbonateHCID 27833462-Bromo-4-fluorobenzoyl chlorideHCID 110307606,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Product 1

HCID 9868852[2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5,11-dihydro-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)-methanoneYield 59.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine of Example 1, Step B (5.15 g, 26.1 mmol) in dimethylformamide (70 mL) under nitrogen was added potassium carbonate (7.95 g, 57.51 mmol). The mixture was cooled and treated dropwise with a solution of crude 2-bromo4-fluorobenzoyl chloride of Step A (31.37 mmol) in dimethylformamide (30 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 to give a brown solid foam. The crude material was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with a hexane-ethyl acetate gradient (from 95:5 to 75:25) provided the pure title compound (6.18 g, 59.5%) along with some impure material (1.2 g). The pure material was triturated with hexane to provide an off-white solid foam, which was 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. customto give a brown solid foam
  6. customabsorbed onto a silica Merck-60 flash column
  7. washElution with a hexane-ethyl acetate gradient (from 95:5 to 75:25)

Sources & evidence

ORD record
ord-fa3c8c29f8ab4892b4351ff04bbdcc96
Source dataset
uspto-grants-2001_02
Patent number
US06194407B1

Linked notes

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