1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (3R,10S)-N-benzyloxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.013,18]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanamide

HRID 849727Notes

Reaction equation

HRID 849727 reaction equation
[CH3:1][CH:2]([CH3:32])[CH2:3][C@@H:4]([C:9](=[O:31])[NH:10][C@H:11]1[CH2:28][C:27]2=[CH:29][N:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=32)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:12]1=[O:30])[CH2:5][C:6]([OH:8])=O.[CH2:33]([O:40][NH2:41])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH2:33]([O:40][NH:41][C:6](=[O:8])[CH2:5][C@H:4]([C:9](=[O:31])[NH:10][C@H:11]1[CH2:28][C:27]2=[CH:29][N:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=32)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][NH:13][C:12]1=[O:30])[CH2:3][CH:2]([CH3:32])[CH3:1])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 102313O-BenzylhydroxylamineHCID 52893145-Methyl-3-(9-oxo-1,8-diaza-tricyclo(10.6.1.013,18)nonadeca-12(19),13,15,17-tetraen-10-ylcarbamoyl)-hexanoic acid

Product 1

HCID 86752868(3R,10S)-N-benzyloxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.013,18]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanamideYield 84.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Alternatively, to a solution of (3R,10S)-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanoic acid (2.5 g, 5.82 mmol), HOBtH2O(0.89 g, 1 eq.) and O-benzyl hydroxylamine (2.2 mL, 3 eq.) in DMF (200 mL) at 0° C. was added EDCI (2.77 g, 2.5 eq.). The resulting mixture was then stirred overnight. DHF was removed by pump distillation at 65° C. To the residue was then added methanol (14 mL) followed by ether (140 mL). With stirring at 0° C., 0.5 N HCl (140 mL) was added, followed by petroleum ether (140 mL). The mixture was stirred at 0° C. for 15 minutes, then the white solid was suction filtered and subsequently washed with water (100 mL) followed by 1:1 ether/petroleum ether (100 mL). Drying under vacuum (P2O5) for 3 hours gave (3R,10S)-N-benzyloxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6.1.0 13,18 ]-nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanamide as a white solid (2.7 g, 84.9%).

Workup

  1. customDHF was removed by pump distillation at 65° C
  2. stirringWith stirring at 0° C.
  3. addition0.5 N HCl (140 mL) was added
  4. stirringThe mixture was stirred at 0° C. for 15 minutes
  5. filtrationthe white solid was suction filtered
  6. washsubsequently washed with water (100 mL)
  7. dry with materialDrying under vacuum (P2O5) for 3 hours

Sources & evidence

ORD record
ord-915af3df7cce4e96898b0c323d611096
Source dataset
uspto-grants-2000_01
Patent number
US06013792

Reaction notes

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