2,6-Dimethylthiophenol → 1-(4-(5-(5-(2,6-Dimethylphenylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone

HRID 1809596Notes

Reaction equation

HRID 1809596 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:23][C:24]2[C:25]([CH3:30])=[N:26][CH:27]=[CH:28][CH:29]=2)[C:5]([NH:8][C:9]2[S:13][N:12]=[C:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH3:21])[CH2:16][CH2:15]3)[N:10]=2)=[N:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:81][C:82]1[CH:87]=[CH:86][CH:85]=[C:84]([CH3:88])[C:83]=1[SH:89]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:81][C:82]1[CH:87]=[CH:86][CH:85]=[C:84]([CH3:88])[C:83]=1[S:89][C:2]1[CH:3]=[C:4]([O:23][C:24]2[C:25]([CH3:30])=[N:26][CH:27]=[CH:28][CH:29]=2)[C:5]([NH:8][C:9]2[S:13][N:12]=[C:11]([CH:14]3[CH2:19][CH2:18][N:17]([C:20](=[O:22])[CH3:21])[CH2:16][CH2:15]3)[N:10]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 610452,6-DimethylthiophenolHCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 250997731-(4-(5-(5-Bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone

Product 1

HCID 250997741-(4-(5-(5-(2,6-Dimethylphenylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanoneYield 46.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

1-(4-(5-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone (0.10 g, 0.20 mmol), xantphos (0.059 g, 0.10 mmol), K3PO4 (0.11 g, 0.53 mmol), and Pd2dba3 (0.047 g, 0.051 mmol) were diluted in degassed toluene (2 mL). 2,6-dimethylbenzenethiol (0.041 mL, 0.31 mmol) was added and the reaction stirred at 110° C. overnight. The solution was cooled and flash chromatographed (10% MeOH/EtOAc) to give 1-(4-(5-(5-(2,6-dimethylphenylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone (0.051 g, 46% yield) as a tan solid. 1H NMR (CDCl3) δ 1.77-1.94 (m, 4H), 2.10 (s, 3H), 2.38 (s, 6H), 2.43 (s, 3H), 2.80 (t, 1H), 3.04 (t, 1H), 3.20 (t, 1H), 3.88 (s, 1H), 4.53 (d, 1H), 6.53 (s, 1H), 7.13-7.23 (m, 5H), 7.64 (s, 1H), 8.42 (s, 1H), 9.02 (bs, 1H).

Workup

  1. temperatureThe solution was cooled
  2. customflash chromatographed (10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-47fe01b25ae1453aba26e286993950c1
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

Loading…