Trifluoroacetic acid → n-[(1r)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]-phenyl}piperidyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide

HRID 489702Notes

Reaction equation

HRID 489702 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([C@@H:32]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][N:33]2C(OC(C)(C)C)=O)=[O:31])[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][C:25]([NH:27][CH3:28])=[O:26])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([C@@H:32]2[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34][NH:33]2)=[O:31])[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][C:25]([NH:27][CH3:28])=[O:26])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 23587443tert-Butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]phenyl}piperidyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 10210174n-[(1r)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]-phenyl}piperidyl)-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared according to the procedure described in Example 3 (Step b) using tert-butyl 3-{N-[(1R)-1[(4-chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]phenyl}piperidyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Step a) (397 mg, 0.59 mmol) and 50% TFA in CH2Cl2 (20 mL). Purification by reverse phase preparative HPLC [Phenomenex; 5 μm 250×21.2 mm, 5% to 95% CH3CN (0.1% TFA) in H2O (0.1% TFA) over 30 min, then 100% CH3CN (0.1% TFA) for 2 min] provided the title compound (TFA salt) as a white foam (266 mg). MS (ESI, pos. ion) m/z: 574 (M+1); (ESI, neg. ion) in/z: 572 (M−1). Calc'd for C32H36ClN5O3: 573.25. Anal. Calcd for C32H36ClN5O3.1.8C2HF3O2: C, 54.86; H. 4.89; N, 8.99. Found: C, 55.11; H, 5.04; N, 9.11.

Workup

  1. customThe title compound was prepared
  2. customPurification by reverse phase preparative HPLC [Phenomenex

Sources & evidence

ORD record
ord-2c5fdab817a4483c8fab4495c6512faf
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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