Cyclohexanecarboxaldehyde → (+/-)-6-[4-(1-Cyclohexylmethyl-piperidin-3-yl)-phenoxy]-nicotinamide

HRID 228203Notes

Reaction equation

HRID 228203 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[CH:23]=[CH:22][C:11]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:10][CH:9]=2)[CH2:3]1.[CH:24]1([CH:30]=O)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[BH4-].[Na+]>>[CH:24]1([CH2:30][N:2]2[CH2:7][CH2:6][CH2:5][CH:4]([C:8]3[CH:9]=[CH:10][C:11]([O:12][C:13]4[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=4)=[CH:22][CH:23]=3)[CH2:3]2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

4

Reactant 3

HCID 16275CyclohexanecarboxaldehydeHCID 4311764Sodium borohydrideHCID 68747046(+/-)-6-(4-Piperidin-3-yl-phenoxy)-nicotinamide hydrochloride2×

Product 1

HCID 59730407(+/-)-6-[4-(1-Cyclohexylmethyl-piperidin-3-yl)-phenoxy]-nicotinamideYield 19%

Procedure

Combine 6-(4-Piperidin-3-yl-phenoxy)-nicotinamide (free base of compound of example 322) (0.96 mL of 0.12 M stock solution in methanol, 0.0344 g, 0.116 mmol) and cyclohexanecarboxaldehyde (0.021 mL, 0.173 mmol), and stir overnight. Add sodium borohydride (0.0108 g, 0.285 mmol), stir for 4.5 h, then concentrate and purify by silica gel chromatography (20:1→10:1 ethyl acetate:methanol) to provide 0.0085 g (19%) of the title compound as a white solid: high resolution mass spectrum (electrospray): m/z calc for C24H32N3O2 394.2495, found 394.2488; 1H NMR (CDCl3): 8.58 (s, 1H), 8.14 (d, 1H, J=7.8 Hz), 7.27 (d, 2H, J=8.3 Hz), 7.05 (d, 2H, J=7.8 Hz), 6.93 (d, 1H, J=8.8 Hz), 5.89 (s br, 2H), 2.99-2.77 (m, 3H), 2.16-2.06 (m, 2H), 1.97-1.83 (m, 3H), 1.80-1.59 (m, 7H), 1.54-1.34 (m, 2H), 1.29-1.03 (m, 5H), 0.93-0.77 (m, 3H).

Workup

  1. concentrationconcentrate
  2. custompurify by silica gel chromatography (20:1→10:1 ethyl acetate:methanol)

Sources & evidence

ORD record
ord-f3391aee47fe41ebb7987696825ed6ed
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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