O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide

HRID 717093Notes

Reaction equation

HRID 717093 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[C:5]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1)[NH:6][C:7]2=[O:12].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(Cl)Cl.[CH3:56][NH:57][CH2:58][CH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>CN(C=O)C>[CH3:56][N:57]([CH2:58][CH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1)[C:17](=[O:19])[C:16]1[CH:15]=[CH:14][C:13]([C:5]2[NH:6][C:7](=[O:12])[C:8]3[C:3]([CH:4]=2)=[C:2]([CH3:1])[CH:11]=[CH:10][CH:9]=3)=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21638731diisopropylethylamine CH2Cl2HCID 22225668Tetrahydro-N-methyl-2H-pyran-4-methanamineHCID 89812882HCID 89812882, compound

Product 1

HCID 117992726N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamideYield 49.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acid (35 mg, 0.125 mmol), TBTU (40 mg, 0.125 mmol) was added 0.36M N,N-diisopropylethylamine/CH2Cl2 (0.35 mL, 0.125 mmol) and anhydrous DMF (0.9 mL). The reaction mixture was stirred at RT for 45 min after which time methyl-(tetrahydro-pyran-4-ylmethyl)-amine (19 mg, 0.15 mmol) in anhydrous DMF (0.45 mL) was added and the reaction mixture was stirred at RT overnight. The reaction mixture was passed through a Si—NH2 cartridge (1 g), eluting with DMF (2× column volumes), MeOH (2× column volumes) and the solvent removed in vacuo and the crude product purified by reverse phase preparative HPLC-MS to obtain N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide as a yellow foam (24 mg, 48%).

Workup

  1. additionwas added
  2. washeluting with DMF (2× column volumes), MeOH (2× column volumes)
  3. customthe solvent removed in vacuo
  4. customthe crude product purified by reverse phase preparative HPLC-MS

Sources & evidence

ORD record
ord-6477bcc247a343adac91b1296735e3b6
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

Loading…