Acetic Acid → 3-({4-[(2R)-2-methyl-1-pyrrolidinyl]-1-piperidinyl}methyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

HRID 245257Notes

Reaction equation

HRID 245257 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)[C:9]([CH2:25][N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1)=[C:8]2[C:33]([NH:35][C@H:36]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:37]([F:40])([F:39])[F:38])=[O:34])(=[O:4])=[O:3].C(O)(=O)C.[CH3:51][C@H:52]1[CH2:56][CH2:55][CH2:54][NH:53]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH3:51][C@@H:52]1[CH2:56][CH2:55][CH2:54][N:53]1[CH:29]1[CH2:28][CH2:27][N:26]([CH2:25][C:9]2[C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)=[N:11][C:12]3[C:7]([C:8]=2[C:33]([NH:35][C@H:36]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:37]([F:40])([F:39])[F:38])=[O:34])=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:14][CH:13]=3)[CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 6999702(2S)-2-methylpyrrolidineHCID 866756106-(methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

Product 1

HCID 534764503-({4-[(2R)-2-methyl-1-pyrrolidinyl]-1-piperidinyl}methyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamideYield 34.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-(Methylsulfonyl)-3-[(4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.093 g, 0.140 mmol) was dissolved in dichloromethane (1.4 mL) and acetic acid (0.012 mL, 0.210 mmol). (S)-2-Methylpyrrolidine (0.036 g, 0.420 mmol) was added followed by sodium triacetoxyborohydride (59.4 mg, 0.280 mmol). The mixture was stirred at room temperature for 2 d. The solvent was removed under reduced pressure, and the residue was purified via HPLC (Waters, Sunfire 30×100 mm, 26-60% CH3CN/H2O with 0.1% TFA) to afford 3-({4-[(2R)-2-methyl-1-pyrrolidinyl]-1-piperidinyl}methyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.035 g, 32% yield). MS (m/z) 733.3 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified via HPLC (Waters, Sunfire 30×100 mm, 26-60% CH3CN/H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-219a1be558ad4a3bac3f9e29380e0d56
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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