Sodium Carbonate → 3-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methyl-phenyl]-2-methyl-cyclohex-2-enone

HRID 1793972Notes

Reaction equation

HRID 1793972 reaction equation
[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12.FC(F)(F)S([O:38][C:39]1[CH2:44][CH2:43][CH2:42][C:41](=O)[C:40]=1[CH3:46])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:20][C:21]1[CH:22]=[C:17]([C:15]([N:7]2[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[CH2:10][N:4]3[CH:3]=[CH:2][CH:1]=[C:5]3[CH2:6]2)=[O:16])[CH:18]=[CH:19][C:32]=1[C:41]1[CH2:42][CH2:43][CH2:44][C:39](=[O:38])[C:40]=1[CH3:46]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 10825071Methanesulfonic acid, trifluoro-, 2-methyl-3-oxo-1-cyclohexen-1-yl esterHCID 22219714(10,11-Dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepin-10-yl)-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone

Product 1

HCID 102950443-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methyl-phenyl]-2-methyl-cyclohex-2-enoneYield 54.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone of Example 2 Step B (6.75 g, 15.8 mmol), 3-oxo-2-methylcyclohexen-1-yl trifluoromethanesulfonate (4.49 g, 17.4 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.387 g, 0.474 mmol) were combined in dimethylsulfoxide (79 mL). Aqueous sodium carbonate (2M, 39.5 mL, 79.0 mmol) was added and the reaction heated to 60° C. for 3 hours. After cooling to room temperature, the reaction mixture was diluted with water and washed with ethyl acetate. The combined extracts were washed with water and brine. The organic phase was dried over anhydrous sodium sulfate, filtered through silica gel and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexane to provide 3.55 g of the title compound as a pale orange foam.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with ethyl acetate
  3. washThe combined extracts were washed with water and brine
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. filtrationfiltered through silica gel
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1a4596afae304eaf88b6df8fc29bc4d2
Source dataset
uspto-grants-2006_04
Patent number
US07022699B2

Reaction notes

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