Triethylamine → 2-tert-butoxycarbonylamino-N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-3-phenylpropionamide

HRID 862405Notes

Reaction equation

HRID 862405 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[C:14]([O:15][CH3:16])=[CH:13][C:12]([CH3:17])=[CH:11][C:10]=2[O:18][CH3:19])[C:6]2[CH:20]=[CH:21][CH:22]=[CH:23][C:5]=2[N:4]([CH3:24])[C:3]1=[O:25].[C:26]([NH:33][C@@H:34]([C:42](O)=[O:43])[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.O>[C:29]([O:28][C:26]([NH:33][CH:34]([CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[C:42]([NH:1][CH:2]1[N:8]=[C:7]([C:9]2[C:14]([O:15][CH3:16])=[CH:13][C:12]([CH3:17])=[CH:11][C:10]=2[O:18][CH3:19])[C:6]2[CH:20]=[CH:21][CH:22]=[CH:23][C:5]=2[N:4]([CH3:24])[C:3]1=[O:25])=[O:43])=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 637610Boc-D-phenylalanineHCID 153796223-Amino-1,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-1,4-benzodiazepin-2-one

Product 1

HCID 190629782-tert-butoxycarbonylamino-N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-3-phenylpropionamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

1.73 g of 3-amino-1,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-1,4-benzodiazepin-2-one are dissolved in 30 ml of dimethylformamide in the presence of 1.42 g of BOC-D-phenylalanine, followed by cooling to 5° C. and addition of 1.07 ml of triethylamine and then 2.4 g of BOP. The reaction mixture is allowed to return to room temperature and is left stirring overnight. It is then poured into water and extracted with ethyl acetate. The organic phase is washed with water, separated out after settling of the phases, dried over Na2SO4, filtered and concentrated under vacuum. An oily residue of 2-tert-butoxycarbonylamino-N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-3-phenylpropionamide, obtained in quantitative yield, is used as it is for the following step (Compound 16).

Workup

  1. customto return to room temperature
  2. waitis left
  3. extractionextracted with ethyl acetate
  4. washThe organic phase is washed with water
  5. customseparated out
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-47addc0814dc4c3299522385b450bc2c
Source dataset
uspto-grants-1998_02
Patent number
US05719143

Reaction notes

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