Methanol → N-[2-({(3R)-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 564360Notes

Reaction equation

HRID 564360 reaction equation
[O:1]=[C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)[CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.CO.[CH3:25][O:26][C:27]1[N:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][C:34]2=O)=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCl>[CH3:25][O:26][C:27]1[N:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH:36]([N:20]3[CH2:21][CH2:22][C@@H:18]([NH:17][C:2](=[O:1])[CH2:3][NH:4][C:5](=[O:16])[C:6]4[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:14])([F:15])[F:13])[CH:7]=4)[CH2:19]3)[CH2:35][CH2:34]2)=[CH:29][CH:28]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 670043421-(6-Methoxypyridin-3-yl)piperidinone

Product 1

HCID 16722463N-[2-({(3R)-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (306 mg, 0.97 mmol; prepared according to WO2004/050024A2) in methanol (757 μL, 1.87 mmol) at room temperature was added 1-(6-methoxypyridin-3-yl)piperidinone (200 mg, 0.971 mmol) followed by sodium triacetoxyborohydride (247 mg, 1.16 mmol); the reaction mixture was stirred for 16 hours. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3R)-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (465 mg, 95%) as a white solid. 1H-NMR (CD3OD) δ: 1.59-1.86 (m, 3H), 2.00-2.14 (m, 2H), 2.21-2.48 (m, 2H), 2.64-2.84 (m, 4H), 2.95-3.10 (m, 2H), 3.26-3.38 (m, 2H), 3.49-3.60 (m, 2H), 3.84 (s, 3H), 4.03 (s, 2H), 4.36-4.48 (m, 1H), 6.73 (d, J=9.3 Hz, 1H), 7.46 (dd, J=9.0, 3.0 Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.76 (d, J=3.0 Hz, 1H), 7.87 (d, J=7.8 Hz, 1H), 8.14 (d, J=8.1 Hz 1H), 8.22 (s, 1H). MS m/z: 506 (M+1).

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-392a5474539b47448531d437794403e2
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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