Sodium hydride → HCID 9887157, compound

HRID 1978187Notes

Reaction equation

HRID 1978187 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.[F: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>[F: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 21996864HCID 21996864, compoundHCID 178428694HCID 178428694, compound

Product 1

HCID 9887157HCID 9887157, compound

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 0.48 g, 12.0 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (60 mL). Neat 3-methylpyrazole (0.48 mL, 6.0 mmol) was added. Stirring was continued until the gas evolution subsided. The (2,4-difluoro-phenyl)-(6,11-dihydro-1H-pyrido[2,3-b][1,5]benzodiazepin-10-yl)-methanone of Step B (2.0 g, 5.9 mmol) was added in one portion to the clear solution. The mixture was placed in an oil bath (preheated at 130° C.) for 1 hour, cooled and partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The crude material was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with hexane-ethyl acetate (gradient from 9:1 to 1:1) provided the title compound along with the more polar 4-fluoro regioisomer of Example 9. The title compound (0.30 g) was obtained as a foam which crystallized by sonication from hexane-ethanol, m.p. 122-125° C.

Workup

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

Sources & evidence

ORD record
ord-eba8cecf8ec6499fa9acf0bed7410ded
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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