Hydrochloric Acid → HCID 70245873, compound

HRID 1976259Notes

Reaction equation

HRID 1976259 reaction equation
[OH:1][C@H:2]1[CH2:11][N:10]2[C@@H:4]([CH2:5][N:6]([C:16](=[O:38])[C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:37])[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:19][CH:18]=3)[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9]2)[CH2:3]1.C1(N=C=NC2CCCCC2)CCCCC1.FC(F)(F)C(O)=O.[ClH:61]>CS(C)=O>[ClH:61].[C:31]1([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24]([NH:23][C:20]2[CH:21]=[CH:22][C:17]([C:16]([N:6]3[C:7]4[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=4[CH2:9][N:10]4[CH2:11][C:2](=[O:1])[CH2:3][C@@H:4]4[CH2:5]3)=[O:38])=[CH:18][CH:19]=2)=[O:37])[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 10868DicyclohexylcarbodiimideHCID 59954345HCID 59954345, compound

Product 1

HCID 70245873HCID 70245873, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (2R,11aR)-2-hydroxy-10-[4-[(2-phenylbenzoyl)amino]benzoyl]-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.4 g) prepared in Example 45 and obtained in the form of free base in dimethyl sulfoxide (8 ml), there was added, at room temperature, 1.6 g of N,N′-dicyclohexyl carbodiimide and 0.135 g of trifluoroacetic acid. After stirring the reaction solution at room temperature for 15 hours, a 6N hydrochloric acid solution was added thereto and the reaction solution was stirred for additional 30 minutes. The precipitates separated out were filtered off and washed with water. The filtrate and the wash liquid were combined, the mixture was alkalified with a saturated aqueous solution of sodium carbonate and then extracted with ethyl acetate. The resulting organic phase was washed with water, dried over anhydrous magnesium sulfate and then concentrated. The resulting residue was subjected to silica gel column chromatography and then eluted with chloroform/acetone (4/1) to thus give 0.23 g of (11aR)-10-[4-[(2-phenylbenzoyl)amino]benzoyl]-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-2-one in the form of amorphous powder. The resulting amorphous powder (0.23 g) was dissolved in ethyl acetate and 0.12 ml of a 4N hydrochloric acid-ethyl acetate solution was added to the resulting solution at room temperature. After stirring the mixture at room temperature for one hour, the resulting precipitates separated out were recovered by filtration, followed by washing them with ethyl acetate and then dried to thus give 0.15 g (yield 34.2%) of the title compound.

Workup

  1. additionthere was added, at room temperature
  2. stirringthe reaction solution was stirred for additional 30 minutes
  3. customThe precipitates separated out
  4. filtrationwere filtered off
  5. washwashed with water
  6. extractionextracted with ethyl acetate
  7. washThe resulting organic phase was washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. washeluted with chloroform/acetone (4/1) to thus give 0.23 g of (11aR)-10-[4-[(2-phenylbenzoyl)amino]benzoyl]-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-2-one in the form of amorphous powder
  11. dissolutionThe resulting amorphous powder (0.23 g) was dissolved in ethyl acetate
  12. addition0.12 ml of a 4N hydrochloric acid-ethyl acetate solution was added to the resulting solution at room temperature
  13. stirringAfter stirring the mixture at room temperature for one hour
  14. customthe resulting precipitates
  15. customseparated out
  16. filtrationwere recovered by filtration
  17. washby washing them with ethyl acetate

Sources & evidence

ORD record
ord-cf8713dbd2ed4c27932de374eda5f08a
Source dataset
uspto-grants-2001_05
Patent number
US06225306B1

Reaction notes

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