Sodium hydride → 4-(2,4-dichlorophenyl)-5-methyl-2-[N-(alpha-cyclopropylbenzyl)-N-(2-tetrahydropyranyloxyethyl)amino]thiazole

HRID 1450262Notes

Reaction equation

HRID 1450262 reaction equation
Br[CH:2]([CH3:13])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:6]=1[Cl:12])=O.[CH:14]1([CH:17]([NH:24][C:25]([NH2:27])=[S:26])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15]1.[H-].[Na+].Br[CH2:31][CH2:32][O:33][CH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][O:35]1>CN(C)C=O.C(OCC)(=O)C.O>[Cl:12][C:6]1[CH:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:27]=[C:25]([NH:24][CH:17]([CH:14]2[CH2:16][CH2:15]2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[S:26][C:2]=1[CH3:13].[Cl:12][C:6]1[CH:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:27]=[C:25]([N:24]([CH:17]([CH:14]2[CH2:15][CH2:16]2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:31][CH2:32][O:33][CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][O:35]2)[S:26][C:2]=1[CH3:13]

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 109239912-Bromo-1-(2,4-dichlorophenyl)propan-1-one2×HCID 18967761N-(alpha-cyclopropylbenzyl)thiourea2×

Product 2

HCID 152916244-(2,4-dichlorophenyl)-5-methyl-2-[N-(alpha-cyclopropylbenzyl)-N-(2-tetrahydropyranyloxyethyl)amino]thiazoleHCID 189678364-(2,4-Dichlorophenyl)-5-methyl-2-[N-(alpha-cyclopropylbenzyl)amino]thiazole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

4-(2,4-Dichlorophenyl)-5-methyl-2-[N-(α-cyclopropylbenzyl)amino]thiazole was prepared from 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1) and N-(α-cyclopropylbenzyl)thiourea (Compound 74) according to the process described in Example 1, Step A. 4 g of this compound is dissolved in 60 ml of anhydrous dimethylformamide and the solution is cooled to 5° C., followed by portionwise addition of 493 mg of sodium hydride. After stirring for one hour at room temperature, 3.14 g of 1-bromo-2-(2-tetrahydropyranyloxy)ethane dissolved in 30 ml of dimethylformamide are added dropwise thereto. The mixture is left stirring for 3 hours. After addition of water and extraction with ethyl acetate, the organic phase is washed with water, dried over anhydrous sodium sulphate and evaporated to dryness. The residue is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent. The expected product is thus obtained.

Workup

  1. additionare added dropwise
  2. waitThe mixture is left
  3. stirringstirring for 3 hours
  4. washthe organic phase is washed with water
  5. dry with materialdried over anhydrous sodium sulphate
  6. customevaporated to dryness
  7. customThe residue is purified on a column of silica
  8. additiona mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent

Sources & evidence

ORD record
ord-02adcae24fce4cb991cef41b04e4530c
Source dataset
uspto-grants-1997_02
Patent number
US05602132

Reaction notes

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