Diisopropylethylamine → N-[4-Cyano-1-(3-ethoxy-4-methyl-benzyl)-piperidin-4-yl]-5-methyl-nicotinamide

HRID 913336Notes

Reaction equation

HRID 913336 reaction equation
Cl.Cl.[C:3]([C:5]1([NH:11][C:12](=[O:20])[C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[N:15][CH:14]=2)[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)#[N:4].[CH2:21]([O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[CH3:32])[CH:27]=O)[CH3:22].C(N(C(C)C)C(C)C)C.C([BH3-])#N.[Na+]>C(O)(C)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[C:3]([C:5]1([NH:11][C:12](=[O:20])[C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[N:15][CH:14]=2)[CH2:10][CH2:9][N:8]([CH2:27][C:26]2[CH:29]=[CH:30][C:31]([CH3:32])=[C:24]([O:23][CH2:21][CH3:22])[CH:25]=2)[CH2:7][CH2:6]1)#[N:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 252420583-Ethoxy-4-methylbenzaldehydeHCID 67401536N-(4-Cyano-piperidin-4-yl)-5-methyl-nicotinamide dihydrochloride

Product 1

HCID 25118793N-[4-Cyano-1-(3-ethoxy-4-methyl-benzyl)-piperidin-4-yl]-5-methyl-nicotinamide

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 3776IsopropanolSolvent

Procedure

To a solution of N-(4-cyano-piperidin-4-yl)-5-methyl-nicotinamide dihydrochloride (171.0 mg, 0.54 mmol, 1.0 equiv) in isopropanol (5 mL) was added 3-ethoxy-4-methyl-benzaldehyde (88.7 mg, 0.54 mmol, 1.0 equiv; intermediate B10), titanium tetra-isopropoxide (766.5 mg, 2.70 mmol, 5.0 equiv) and N-ethyl diisopropylamine (209.5 mg, 1.62 mmol, 3.0 equiv), followed by sodium cyanoborohydride (67.4 mg, 1.08 mmol, 2.0 equiv) after stirring for 1 h. The reaction mixture was allowed to react overnight and then poured directly onto a silica column eluting with ethyl acetate. The isolated crude product was purified by a second silica column eluting with dichloromethane/methanol (93:7) delivered finally 22.0 mg (24%) of the title compound as colorless oil. MS (ISP): 393.2 [M+H]+.

Workup

  1. customto react overnight
  2. additionpoured directly onto a silica column
  3. washeluting with ethyl acetate
  4. customThe isolated crude product
  5. customwas purified by a second silica column
  6. washeluting with dichloromethane/methanol (93:7)

Sources & evidence

ORD record
ord-b92a124839f34ecaa2e8b318640cfb64
Source dataset
uspto-grants-2011_09
Patent number
US08026365B2

Reaction notes

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