Triethylamine → (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-[4-(tetrahydropyran-4-yl)-piperazin-1-yl]-butane-1,4-dione

HRID 643103Notes

Reaction equation

HRID 643103 reaction equation
[NH2:1][C:2]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][C:5]([CH2:6][C@@H:7]([CH2:11][C:12](=[O:31])[N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)[C:8]([OH:10])=O)=[CH:4][C:3]=1[Cl:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[O:68]1[CH2:73][CH2:72][CH:71]([N:74]2[CH2:79][CH2:78][NH:77][CH2:76][CH2:75]2)[CH2:70][CH2:69]1.C([O-])(O)=O.[Na+]>C1COCC1>[NH2:1][C:2]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][C:5]([CH2:6][C@@H:7]([CH2:11][C:12]([N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[CH2:25][CH2:24][C:23]4[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=4[NH:21][C:20]3=[O:30])[CH2:15][CH2:14]2)=[O:31])[C:8]([N:77]2[CH2:76][CH2:75][N:74]([CH:71]3[CH2:72][CH2:73][O:68][CH2:69][CH2:70]3)[CH2:79][CH2:78]2)=[O:10])=[CH:4][C:3]=1[Cl:38]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 219423151-(Oxan-4-yl)piperazineHCID 68591515(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid

Product 1

HCID 11992972(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-1-[4-(tetrahydropyran-4-yl)-piperazin-1-yl]-butane-1,4-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 100 mg (0.18 mmol) (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid, 65 mg (0.20 mmol) TBTU and 35 μL (0.18 mmol) triethylamine in 10 mL THF was stirred for 1 h at RT. Then 40 mg (0.24 mmol) 1-(tetrahydropyran-4-yl)-piperazine was added and the reaction solution was stirred overnight. 20 mL semisaturated NaHCO3 solution was added, extracted twice with 40 mL EtOAc and the combined organic phases were dried over Na2SO4. After the desiccant and solvent had been eliminated the residue was purified by HPLC; the fractions containing the product were combined and lyophilised.

Workup

  1. additionwas added
  2. extractionextracted twice with 40 mL EtOAc
  3. dry with materialthe combined organic phases were dried over Na2SO4
  4. customwas purified by HPLC
  5. additionthe fractions containing the product

Sources & evidence

ORD record
ord-841fc3a3e0b74af09dfe6186965311b0
Source dataset
uspto-grants-2010_04
Patent number
US07696209B2

Reaction notes

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