Triethylamine → 2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(3,3-difluoropiperidin-1-yl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

HRID 1968329Notes

Reaction equation

HRID 1968329 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][OH:19])=[CH:12][CH:11]=2)[C:5]([C:20]#[N:21])=[C:4]([S:22][CH2:23][C:24]2[N:25]=[C:26]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[S:27][CH:28]=2)[N:3]=1.Cl.[F:37][C:38]1([F:44])[CH2:43][CH2:42][CH2:41][NH:40][CH2:39]1.C(N(CC)CC)C>C1COCC1.O>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([C:26]2[S:27][CH:28]=[C:24]([CH2:23][S:22][C:4]3[C:5]([C:20]#[N:21])=[C:6]([C:10]4[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH2:18][OH:19])=[CH:14][CH:15]=4)[C:7]([C:8]#[N:9])=[C:2]([N:40]4[CH2:41][CH2:42][CH2:43][C:38]([F:44])([F:37])[CH2:39]4)[N:3]=3)[N:25]=2)=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27583493,3-Difluoropiperidine hydrochlorideHCID 866438472-Chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Product 1

HCID 687629952-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(3,3-difluoropiperidin-1-yl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

At RT, 150 mg (0.20 mmol, purity about 74%) of 2-chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), 64 mg (0.41 mmol) of 3,3-difluoropiperidine hydrochloride and 57 μl (0.41 mmol) of triethylamine were stirred in 3 ml of THF for 2 h. The reaction mixture was then diluted with about 1 ml of water and about 3 ml of THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 90 mg (71% of theory) of the target compound.

Workup

  1. custompurified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-b565d751836640738451082e40217570
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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