Dimethylformamide → (11aS)-10-[4-[(2-Phenylbenzoyl) Amino]Benzoyl]-1,2,3,10,11, 11a-Hexahydro-5H-Pyrrolo[2,1-c][1,4]Benzodiazepin-5-One

HRID 1976248Notes

Reaction equation

HRID 1976248 reaction equation
[C:1]1([C:7]2[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=2[C:9]([NH:11][C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.CN(C)C=O.[CH2:34]1[C@H:38]2[CH2:39][NH:40][C:41]3[CH:48]=[CH:47][CH:46]=[CH:45][C:42]=3[C:43](=[O:44])[N:37]2[CH2:36][CH2:35]1>O1CCCC1.C(Cl)(Cl)Cl.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]1([C:7]2[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=2[C:9]([NH:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([N:40]3[C:41]4[CH:48]=[CH:47][CH:46]=[CH:45][C:42]=4[C:43](=[O:44])[N:37]4[CH2:36][CH2:35][CH2:34][C@H:38]4[CH2:39]3)=[O:17])=[CH:14][CH:13]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 105435024-[(2-phenylbenzoyl)amino]benzoic AcidHCID 44430444(11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one

Product 1

HCID 10006220(11aS)-10-[4-[(2-Phenylbenzoyl) Amino]Benzoyl]-1,2,3,10,11, 11a-Hexahydro-5H-Pyrrolo[2,1-c][1,4]Benzodiazepin-5-OneYield 44.4%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8471TriethylamineSolventHCID 21584013Chloroform ethylacetateSolvent

Procedure

To a solution of 4-[(2-phenylbenzoyl)amino]benzoic acid (1.44 g) in tetrahydrofuran (10 ml), there were added, with ice-cooling, 0.62 g of thionyl chloride and a catalytic amount of N,N-dimethylformamide and the mixture was stirred at room temperature for one hour. After concentration of the reaction solution, the resulting acid chloride was dissolved in 10 ml of tetrahydrofuran and the resulting solution was dropwise added to a solution of (11aS)-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one (4 g) prepared in Reference Example 24 and triethylamine (0.5 g) in tetrahydrofuran (10 ml) with ice-cooling. The reaction solution was stirred for 2 hours under ice-cooling and it was concentrated and dissolved in ethyl acetate. The resulting organic phase was washed with water and then dried over anhydrous magnesium sulfate. The residue obtained after concentration of the reaction solution was subjected to silica gel column chromatography and then eluted with chloroform/ethyl acetate (100/1) to thus give 0.89 g (yield 44.4%) of the title compound.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. temperaturecooling
  4. concentrationit was concentrated
  5. dissolutiondissolved in ethyl acetate
  6. washThe resulting organic phase was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe residue obtained after concentration of the reaction solution

Sources & evidence

ORD record
ord-6d81fa63d2364c4d9066663c0c0da5cf
Source dataset
uspto-grants-2001_05
Patent number
US06225306B1

Reaction notes

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