1,2-Dichloroethane → (+/-)-6-[4-(3-Cyclohexyl-piperidin-1-ylmethyl)-phenoxy]-nicotinamide hydrochloride

HRID 228240Notes

Reaction equation

HRID 228240 reaction equation
[CH:1]1([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C2CCCNC2)C=CC=CC=1.[CH:25]([C:27]1[CH:42]=[CH:41][C:30]([O:31][C:32]2[CH:40]=[CH:39][C:35]([C:36]([NH2:38])=[O:37])=[CH:34][N:33]=2)=[CH:29][CH:28]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[Cl:61]CCCl>>[ClH:61].[CH:1]1([CH:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:25][C:27]3[CH:42]=[CH:41][C:30]([O:31][C:32]4[CH:40]=[CH:39][C:35]([C:36]([NH2:38])=[O:37])=[CH:34][N:33]=4)=[CH:29][CH:28]=3)[CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 1072073-PhenylpiperidineHCID 38093533-CyclohexylpiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide2×

Product 1

HCID 68777511(+/-)-6-[4-(3-Cyclohexyl-piperidin-1-ylmethyl)-phenoxy]-nicotinamide hydrochlorideYield 37%

Procedure

Using a method similar to Example 345, a mixture of 3-cyclohexyl-piperidine and 3-phenyl piperidine (from step 1 above) (3:1, 0.118 g), 6-(4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.183 g, 0.755 mmol), sodium triacetoxyborohydride (0.247 g, 1.16 mmol), and acetic acid (0.067 mL, 1.17 mmol) in 1,2-dichloroethane (10.0 mL) provides, after reverse-phase HPLC, 0.155 g (37%) of the title compound as a white solid: high resolution mass spectrum (electrospray): m/z calc for C24H32N3O2 394.2495, found 394.2478; 1H NMR (methanol-d4): 8.68 (d, 1H, J=2.4 Hz), 8.38 (dd, 1H, J=2.4, 8.3 Hz), 7.69-7.63 (m, 2H), 7.37-7.32 (m, 2H), 7.18 (d, 1H, J=8.8 Hz), 4.42 (d, 1H, J=13.2 Hz), 4.34 (d, 1H, J=13.2 Hz), 3.62-3.55 (m, 1H), 3.54-3.47 (m, 1H), 2.92 (dt, 1H, J=3.4, 13.2 Hz), 2.84 (t, 1H, J=12.2), 2.08-2.00 (m, 1H), 2.00-1.92 (m, 1H), 1.87-1.66 (m, 7H), 1.39-1.02 (m, 7H).

Workup

  1. customprovides

Sources & evidence

ORD record
ord-67ec9d8544674533aca97483e135dd11
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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