Boc-D-phenylalanine → 3(R,S)-[2(R)-(tert-butyloxycarbonyl)amino-3-phenylpropionylamino]-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 743706Notes

Reaction equation

HRID 743706 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH3:20])[C:3]1=[O:21].[C:22]([NH:29][C@@H:30]([C:38](O)=[O:39])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].O.O.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[C:25]([O:24][C:22]([NH:29][C@H:30]([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:38]([NH:1][CH:2]1[N:8]=[C:7]([CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH3:20])[C:3]1=[O:21])=[O:39])=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 637610Boc-D-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 214804643-amino-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-oneHCID 214804841-Hydroxybenzotriazole trihydrate

Product 1

HCID 1317195563(R,S)-[2(R)-(tert-butyloxycarbonyl)amino-3-phenylpropionylamino]-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3(R,S)-amino-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (4.08 g) in anhydrous dimethyl formamide (30 ml), under an atmosphere of nitrogen, was added in succession Boc-D-phenylalanine (3.98 g), 1-hydroxybenzotriazole trihydrate (2.03 g) and 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (2.88 g). Triethylamine (2.09 ml) was then added and the resulting suspension stirred at ambient temperature for 1 h. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate (100 ml) and 10% citric acid solution (100 ml). The organic phase was separated and the aqueous phase extracted with ethyl acetate (3×50 ml). The combined organic phases were washed with 10% sodium hydroxide solution (100 ml), water (50 ml) and brine (50 ml). The organic layer was separated, dried (Na2SO4) and evaporated in vacuo to afford crude 3(R,S)-[2(R)-(tert-butyloxycarbonyl)amino-3-phenylpropionylamino]-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate (100 ml) and 10% citric acid solution (100 ml)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with ethyl acetate (3×50 ml)
  5. washThe combined organic phases were washed with 10% sodium hydroxide solution (100 ml), water (50 ml) and brine (50 ml)
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-b125c3d00749400c8380277136f57c88
Source dataset
uspto-grants-1996_09
Patent number
US05556969

Reaction notes

Loading…