Sodium hydride → HCID 21996872, compound

HRID 1978190Notes

Reaction equation

HRID 1978190 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.F[C:10]1[CH:11]=[CH:12][C:13]([CH3:33])=[C:14]([C:16]([N:18]2[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[NH:22][C:21]3[N:29]=[CH:30][CH:31]=[CH:32][C:20]=3[CH2:19]2)=[O:17])[CH:15]=1>CCCCCC>[CH3:33][C:13]1[CH:12]=[CH:11][C:10]([N:6]2[CH:7]=[CH:8][C:4]([CH3:3])=[N:5]2)=[CH:15][C:14]=1[C:16]([N:18]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]2[N:29]=[CH:30][CH:31]=[CH:32][C:20]=2[CH2:19]1)=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21996882HCID 21996882, compoundHCID 178428694HCID 178428694, compound

Product 1

HCID 21996872HCID 21996872, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% suspension in oil, 0.25 g, 6.25 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (10 mL). Neat 3-methylpyrazole (0.28 mL, 3.5 mmol) was added in one portion at ambient temperature. Stirring was continued until the gas evolution subsided. The (5-fluoro-2-(methyl)-phenyl)-(6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone of Step B (0.75 g, 1.94 mmol) was added in one portion to the clear solution. The mixture was heated to reflux for 26 hours, cooled and partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with hexane-ethyl acetate (gradient from 8:2 to 7:3) provided the title product (0.55 g) as a pale yellow foam which was crystallized by sonication from hexane-ethanol, m.p. 209-210° C.

Workup

  1. customdried under nitrogen
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 26 hours
  4. temperaturecooled
  5. custompartitioned between water and ethyl acetate
  6. dry with materialThe organic extracts were dried over sodium sulfate
  7. customevaporated to dryness
  8. dissolutionThe residue was dissolved in dichloromethane
  9. customabsorbed onto a silica Merck-60 flash column
  10. washElution with hexane-ethyl acetate (gradient from 8:2 to 7:3)

Sources & evidence

ORD record
ord-fe64795d6d5441e39eb45a00f3f0bf3d
Source dataset
uspto-grants-2001_05
Patent number
US06235900B1

Reaction notes

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