Triethylamine → (R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 599746Notes

Reaction equation

HRID 599746 reaction equation
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:36]([OH:38])=O)[CH2:19][C:20]3[CH:25]=[C:24]([CH3:26])[C:23]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:22]([CH3:35])[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[CH2:72]([N:79]1[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]1)[C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1>C1COCC1.CN(C=O)C.CCOC(C)=O>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C@H:18]([CH2:19][C:20]3[CH:21]=[C:22]([CH3:35])[C:23]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:24]([CH3:26])[CH:25]=3)[C:36]([N:82]3[CH2:83][CH2:84][N:79]([CH2:72][C:73]4[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=4)[CH2:80][CH2:81]3)=[O:38])=[O:16])[CH2:13][CH2:14]2)[CH2:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 759941-BenzylpiperazineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 25208036(R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 67274145(R)-1-(4-benzyloxy-3,5-dimethyl-benzyl)-2-(4-benzyl-piperazin-1-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.54 g (2.69 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 952 mg (2.96 mmol) TBTU and 0.47 mL (3.37 mmol) triethylamine in 10 mL THF and 2 mL DMF the mixture was stirred for 1 h at RT. Then 0.52 mL (2.96 mmol) 1-benzyl-piperazine was added and the reaction mixture was stirred for another 14 h at RT. 30 mL EtOAc were added, the organic phase was washed with semisaturated NaHCO3 solution and dried on Na2SO4. After the elimination of the desiccant and solvent the residue was purified by chromatography (silica gel, EtOAc/Cyc 95:5), the fractions containing the product were combined, evaporated down, the residue was triturated with DIPE, suction filtered and dried.

Workup

  1. washthe organic phase was washed with semisaturated NaHCO3 solution
  2. customdried on Na2SO4
  3. customAfter the elimination of the desiccant and solvent the residue was purified by chromatography (silica gel, EtOAc/Cyc 95:5)
  4. additionthe fractions containing the product
  5. customevaporated down
  6. customthe residue was triturated with DIPE, suction
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-29b00c391dec48d696dc4179f0359efe
Source dataset
uspto-grants-2011_03
Patent number
US07897603B2

Reaction notes

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