1,2-Dichloroethane → HCID 14208219, compound

HRID 1084530Notes

Reaction equation

HRID 1084530 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[NH:4][C:3]1=[O:19].[C:20]([NH:27][C@H:28]([C:36](O)=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C(Cl)CCl.C(N(CC)CC)C>CN(C=O)C>[C:23]([O:22][C:20]([NH:27][C@@H:28]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:36]([NH:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[NH:4][C:3]1=[O:19])=[O:37])=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 42596493-Amino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one

Product 1

HCID 14208219HCID 14208219, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(RS)-Amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (1.3 g, 5.17 mmole), Boc-L-phenylalanine (1.37 g, 5.17 mmole), HBT (0.70 g, 5.17 mmole), and EDC (0.99 g, 5.17 mmole) were combined in DMF (30 ml) and stirred at room temperature. The pH of the mixture was adjusted to 9.5 with triethylamine. After 1/2 hour, the DMF was removed in vacuo and the residue treated with 10% citric acid (10 ml), neutralized with Na2CO3 and extracted with CH2Cl2 (3×15 ml). The combined organic layers were washed with water, dried over Na2SO4, filtered, and evaporated to dryness in vacuo. The residue was chromatographed on silica gel (90/3/0.3/0.3 CH2Cl2 /MeOH/H2O/HOAc) and the combined product fractions evaporated to dryness in vacuo. The residue was dissolved in CH2Cl2 (10 ml), washed with saturated Na2CO3 solution (2 ml), dried over Na2SO4, filtered and evaporated to dryness. The residue was treated with Et2O and evaporated five times to give the title compound as a mixture of diastereomers (m.p. 143-153° C.). TLC: silica gel (90/10/1/1 CH2Cl2 /MeOH/MoAc/H2O), Rf =0.58

Workup

  1. customthe DMF was removed in vacuo
  2. additionthe residue treated with 10% citric acid (10 ml)
  3. extractionextracted with CH2Cl2 (3×15 ml)
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. customThe residue was chromatographed on silica gel (90/3/0.3/0.3 CH2Cl2 /MeOH/H2O/HOAc)
  9. customthe combined product fractions evaporated to dryness in vacuo
  10. dissolutionThe residue was dissolved in CH2Cl2 (10 ml)
  11. washwashed with saturated Na2CO3 solution (2 ml)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customevaporated to dryness
  15. additionThe residue was treated with Et2O
  16. customevaporated five times

Sources & evidence

ORD record
ord-9466477e71144ee28c856e662c4999f2
Source dataset
uspto-grants-1991_04
Patent number
US05004741

Reaction notes

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