Sodium Carbonate → (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-(3,4-dihydro-naphthalen-1-yl)-3-methyl-phenyl]-methanone

HRID 1794007Notes

Reaction equation

HRID 1794007 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[C:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][CH2:41][CH:40]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[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]([C:39]4[C:48]5[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=5)[CH2:42][CH2:41][CH:40]=4)=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 10967830Methanesulfonic acid, trifluoro-, 3,4-dihydro-1-naphthalenyl 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 9867363(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[4-(3,4-dihydro-naphthalen-1-yl)-3-methyl-phenyl]-methanoneYield 90.9%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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 (0.760 g, 1.89 mmol), 3,4-dihydro-naphthalen-1-yl trifluoromethanesulfonate (0.579 g, 2.08 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.046 g, 0.0567 mmol) were combined in N,N-dimethylformamide (9.5 mL). 2 M aqueous sodium carbonate (4.73 mL, 9.45 mmol) was added and the reaction heated to 60° C. for 3 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL) and washed with water and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated and the residue purified by flash column chromatography (silica, 30% ethyl acetate in hexanes). Recrystallization from petroleum ether afforded the title compound (0.740 g) as white crystals identical to the material of Example 31.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water and brine
  3. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue purified by flash column chromatography (silica, 30% ethyl acetate in hexanes)
  7. customRecrystallization from petroleum ether

Sources & evidence

ORD record
ord-bbfd2716e5c346f4a8aedf6373a44fd7
Source dataset
uspto-grants-2006_04
Patent number
US07022699B2

Reaction notes

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