3-Pyridinecarbonyl chloride, hydrochloride (1:1) → 1-(Nicotinoyl)-3-(SR)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

HRID 1276501Notes

Reaction equation

HRID 1276501 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH:14]3[CH:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=1.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:25]([N:16]1[CH2:17][CH:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:14]([CH2:13][N:10]2[CH2:9][CH2:8][CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:12][CH2:11]2)[CH2:15]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=1

Participants

5

Reactant 2

HCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 545487023-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

Product 1

HCID 702019961-(Nicotinoyl)-3-(SR)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidineYield 78.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 20 mg (0.06 mmol) of 3-(RS)-((4-phenyl)-piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine (from Example 30, Step A), 19 mg (0.19 mmol) of TEA and 6 mg (0.05 mmol) of 4-DMAP in 2 mL of CH2Cl2 (2 mL) was treated with 28 mg (0.16 mmol) of nicotinoyl chloride·HCl and was stirred at rt for 2 h. The reaction was concentrated in Vacuo. Preparative thin layer chromatography (silica gel GF, 20×20 cm, 1000 microns) using 92:8 v/v MeOH/CH2Cl2 +0.5% NH4OH as the eluant afforded 20 mg (71%) of the title compound as a yellow foam. 1H NMR (500 MHz, CDCl3): δ7.17-8.88 (9H), 1.27-4.24 (22H). Mass Spectrum (NH3 -CI): 426 (M+1).

Workup

  1. concentrationThe reaction was concentrated in Vacuo

Sources & evidence

ORD record
ord-19eb0cdaf22146a28ef8fac22900b5d6
Source dataset
uspto-grants-2000_12
Patent number
US06166037

Reaction notes

Loading…