Formaldehyde → N-((R)-1-Methylpiperidin-3-yl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445278Notes

Reaction equation

HRID 445278 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]2[C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)=[O:9])[CH2:2]1.C=O.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH3:32][N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8]([N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]2[C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:25]=2)=[O:9])[CH2:2]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59536393N-((R)-Piperidin-3-yl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

Product 1

HCID 59536266N-((R)-1-Methylpiperidin-3-yl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of N—((R)-piperidin-3-yl)-1-(4-(trifluoromethyl)phenyl)-3,4-dihydro-isoquinoline-2(1H)-carboxamide (30 mg, 74 μmol, example 24) in DCE (0.5 mL) was added formaldehyde (28 μL, 372 mol). The resulting mixture was stirred at RT for 1 h and then sodium triacetoxyborohydride (16 mg, 74 μmol) was added. The mixture was then stirred at RT for 4 h. Then, saturated NaHCO3 (0.4 mL) was added and the mixture was extracted with EtOAc (2×3 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was purified by silica gel flash column chromatography (0%-10% MeOH (2M NH3)/EtOAc) to give the title compound as an off-white solid. MS (ESI, positive ion) m/z: 418 (M+H).

Workup

  1. stirringThe mixture was then stirred at RT for 4 h
  2. extractionthe mixture was extracted with EtOAc (2×3 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel flash column chromatography (0%-10% MeOH (2M NH3)/EtOAc)

Sources & evidence

ORD record
ord-01edc37d2fbb414bbc8b5059420bd573
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

Loading…