1,3-Dichloroacetone → 2-Amino-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitrile

HRID 2362825Notes

Reaction equation

HRID 2362825 reaction equation
Cl[CH2:2][C:3]([CH2:5]Cl)=O.[F:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([NH2:17])=[S:16])=[CH:10][CH:9]=1.[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][OH:36])=[CH:29][CH:28]=2)[C:22]([C:37]#[N:38])=[C:21]([SH:39])[N:20]=1.C(=O)(O)[O-].[Na+]>C(O)C.O>[NH2:18][C:19]1[C:24]([C:25]#[N:26])=[C:23]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH2:34][CH2:35][OH:36])=[CH:31][CH:32]=2)[C:22]([C:37]#[N:38])=[C:21]([S:39][CH2:5][C:3]2[N:17]=[C:15]([NH:14][C:11]3[CH:10]=[CH:9][C:8]([F:7])=[CH:13][CH:12]=3)[S:16][CH:2]=2)[N:20]=1

Participants

7

Reactant 4

HCID 107931,3-DichloroacetoneHCID 516892Sodium BicarbonateHCID 6930614-FluorophenylthioureaHCID 178510483HCID 178510483, compound

Product 1

HCID 116205652-Amino-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

244 mg (1.92 mmol) of 1,3-dichloroacetone are added to a solution of 327 mg (1.92 mmol) of 4-fluorophenylthiourea in 8 ml of ethanol, and the mixture is stirred under reflux for 1 h. The mixture is concentrated, the residue is dissolved in 4 ml of DMF, 429 mg (1.37 mmol) of 2-amino-4-[4-(2-hydroxyethoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile (preparation see WO 03/053441, Example 6/Method 1, Step 1) and 346 mg (4.1 mmol) of sodium bicarbonate are added and the mixture is stirred at RT overnight. After addition of water, the precipitate is decanted off and the residue is triturated with dichloromethane. After chromatography on silica gel (mobile phase dichloromethane/methanol 50:1), the title compound is obtained as a yellowish solid.

Workup

  1. temperatureunder reflux for 1 h
  2. concentrationThe mixture is concentrated
  3. dissolutionthe residue is dissolved in 4 ml of DMF
  4. stirringthe mixture is stirred at RT overnight
  5. customthe precipitate is decanted off
  6. customthe residue is triturated with dichloromethane

Sources & evidence

ORD record
ord-5a09220ee5a049b9bc71dc523332c0df
Source dataset
uspto-grants-2014_04
Patent number
US08691850B2

Reaction notes

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