Water → HCID 67503655, compound

HRID 1046978Notes

Reaction equation

HRID 1046978 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+].Cl[CH2:20][C:21](=[O:27])[CH2:22][C:23]([O:25][CH3:26])=[O:24].O>CN(C)C=O>[O:27]=[C:21]([CH2:20][N:6]1[C:7](=[O:16])[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[NH:10][C:11]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]1=2)[CH2:22][C:23]([O:25][CH3:26])=[O:24]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 36240Methyl 4-chloroacetoacetateHCID 701695,11-Dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-one

Product 1

HCID 67503655HCID 67503655, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (0.5 g, 1 eq.) was suspended in dimethylformamide (DMF) (15 mL). The reaction was cooled to 0° C. and sodium hydride (60% in mineral oil) (230 mg, 2.5 eq.) was added. The reaction was warmed to room temperature and stirred until gas evolution ceased. The reaction was cooled to 0° C. and methyl 4-chloro-3-oxobutanoate (0.360 g, 1 eq.) was added. The reaction was stirred at room temperature overnight. The reaction was poured onto 50 mL water and extracted with dichloromethane (2×50 mL). The organic extracts were combined, washed with water (2×50 mL), brine (2×50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure, giving 360 mg of crude product. Additional material was recuperated from the aqueous phase through extraction with ethyl acetate (3×50 mL). The ethyl acetate extracts were combined, washed with water (2×50 mL), brine (2×50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure, giving additional 135 mg of crude product. The crude product, 3-oxo-4-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)butanoate was used without purification. LCMS: 326 [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. extractionextracted with dichloromethane (2×50 mL)
  5. washwashed with water (2×50 mL), brine (2×50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customgiving 360 mg of crude product
  10. extractionAdditional material was recuperated from the aqueous phase through extraction with ethyl acetate (3×50 mL)
  11. washwashed with water (2×50 mL), brine (2×50 mL)
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d6848fd278474032a88530de464d7472
Source dataset
uspto-grants-2013_10
Patent number
US08569331B2

Reaction notes

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