Sodium hydride → [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 636370Notes

Reaction equation

HRID 636370 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.[Br:9][C:10]1[CH:15]=[C:14](F)[CH:13]=[CH:12][C:11]=1[C:17]([N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[NH:23][C:22]2[N:30]=[CH:31][CH:32]=[CH:33][C:21]=2[CH2:20]1)=[O:18]>CCCCCC>[Br:9][C:10]1[CH:15]=[C:14]([N:6]2[CH:7]=[CH:8][C:4]([CH3:3])=[N:5]2)[CH:13]=[CH:12][C:11]=1[C:17]([N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[NH:23][C:22]2[N:30]=[CH:31][CH:32]=[CH:33][C:21]=2[CH2:20]1)=[O:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15513329[2-Bromo-4-fluorophenyl]-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanoneHCID 178428694HCID 178428694, compound

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 46.5%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 1.2 g, 30.15 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (110 mL). Neat 3-methylpyrazole (2.47 g, 30.15 mmol) was added dropwise at 0° C. After the gas evolution subsided the cooling bath was removed and stirring was continued at room temperature. The [2-bromo-4-fluorophenyl]-(5,11-dihydro-pyrido [2,3-b][1,5]benzodiazepin-6-yl)-methanone of Step B (6 g, 18.07 mmol) was added in one portion to the clear solution. The mixture was placed in an oil bath (preheated at 130° C.) for 40 minutes, cooled and partitioned between water and ethyl acetate. The organic extracts were dried over magnesium sulfate and evaporated to dryness. 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 less polar title compound (3.87 g) along with a mixture of 3- and 5-methylpyrazole regioisomers (0.860 g). The title compound (3.5 g, 51%) crystallized by sonication from hexane-ethanol, m.p. 208-209° C. (dec).

Workup

  1. customdried under nitrogen
  2. customwas removed
  3. customwas continued at room temperature
  4. customThe mixture was placed in an oil bath
  5. temperaturecooled
  6. custompartitioned between water and ethyl acetate
  7. dry with materialThe organic extracts were dried over magnesium sulfate
  8. customevaporated to dryness
  9. dissolutionThe crude material was dissolved in dichloromethane
  10. customabsorbed onto a silica Merck-60 flash column
  11. washElution with a hexane-ethyl acetate gradient (from 95:5 to 75:25)

Sources & evidence

ORD record
ord-6fc4119dd1bf480ca02d59f9369f3182
Source dataset
uspto-grants-2001_02
Patent number
US06194407B1

Reaction notes

Loading…