Sodium hydride → tert-butyl (1-(4-(2-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)acetyl)phenyl)cyclobutyl)carbamate

HRID 1046986Notes

Reaction equation

HRID 1046986 reaction equation
[N:1]1[C:11]2[NH:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[C:7](=[O:16])[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1)=[O:22]>CN(C)C=O>[O:16]=[C:7]1[N:6]([CH2:20][C:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:32][CH2:31][CH2:30]3)=[CH:27][CH:28]=2)=[O:22])[C:5]2[CH:4]=[CH:3][CH:2]=[N:1][C:11]=2[NH:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]1=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 701695,11-Dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-oneHCID 86664668Tert-butyl (1-(4-(2-bromoacetyl)phenyl)cyclobutyl)carbamate

Product 1

HCID 69087642tert-butyl (1-(4-(2-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)acetyl)phenyl)cyclobutyl)carbamateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (0.362 g, 1.05 eq.) was suspended in dimethylformamide (DMF) (5 mL). The reaction was cooled to 0° C. and sodium hydride (60% in mineral oil) (0.2 g, 3.0 eq.) was added. The reaction was warmed to room temperature and stirred until gas evolution ceased. The reaction was cooled to 0° C. and tert-butyl (1-(4-(2-bromoacetyl)phenyl)cyclobutyl)carbamate (0.6 g, 1.0 eq.) in DMF (1 mL) was added. The reaction was stirred at room temperature overnight. The reaction was quenched by the addition of aqueous saturated ammonium chloride solution (1 mL). Dichloromethane was added (15 mL) and the phases were separated. The organic phase was washed with water (3×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by column chromatography (50% ethyl acetate in dichloromethane), giving tert-butyl (1-(4-(2-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)acetyl)phenyl)cyclobutyl)carbamate (0.4 g, 50%) as a yellow semi-solid. LCMS: 499 [M+H].

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. temperatureThe reaction was cooled to 0° C.
  3. stirringThe reaction was stirred at room temperature overnight
  4. customThe reaction was quenched by the addition of aqueous saturated ammonium chloride solution (1 mL)
  5. additionDichloromethane was added (15 mL)
  6. customthe phases were separated
  7. washThe organic phase was washed with water (3×10 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe product was purified by column chromatography (50% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-0077da557dfb4858b9367a6987687c54
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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