5-Thiazolecarboxylic acid, 4-methyl-, ethyl ester → 5-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, ethyl ester

HRID 1406817Notes

Reaction equation

HRID 1406817 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].Br[C:13]1[CH:14]=[CH:15][C:16]([O:21][CH2:22][CH:23]([CH3:25])[CH3:24])=[C:17]([CH:20]=1)[C:18]#[N:19]>C1(C)C(C)=CC=CC=1.CS(C)=O.[Pd]>[C:18]([C:17]1[CH:20]=[C:13]([C:4]2[S:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]([CH3:1])[N:3]=2)[CH:14]=[CH:15][C:16]=1[O:21][CH2:22][CH:23]([CH3:25])[CH3:24])#[N:19]

Participants

6

Reactant 2

HCID 2986105-Thiazolecarboxylic acid, 4-methyl-, ethyl esterHCID 665851345-Bromo-2-isobutoxybenzonitrile

Product 1

HCID 98845495-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, ethyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 7237O-XyleneSolvent2×

Conditions

Temperature
140 °C

Procedure

To a test tube-type reaction vessel (60 mL) were added ethyl 4-methylthiazole-5-carboxylate (2.14 g, 12.5 mmol), 5-bromo-2-isobutoxybenzonitrile (2.54 g, 10.0 mmol) obtained in the Reference Example 1 and xylene (7.6 mL). After adding compounds listed in the Table 9 as a palladium compound (0.025 mmol), a ligand (0.10 mmol), a base (21.0 mmol), a carboxylic acid (0.10 mmol), and an additive (1.0 mmol), the reaction vessel was filled with nitrogen gas and sealed air-tight. The reaction mixture was heated to 140° C. and stirred for 24 hours. After the completion of the reaction, a part of the reaction solution was diluted with xylene and DMSO and the resulting solution was analyzed by HPLC measurement. The total HPLC area % of the compound A to D and TM (TM means target compound) was adjusted to 100%, the calculated yield of the subject material was calculated from each HPLC area %. Calculation of the yield from the HPLC area % of the subject material was carried out by applying corresponding numbers in the following calculation formula. Yield (%) of TM=total amount of TM (mol)/[{total amount of A (mol)+total amount of C (mol)×2+total amount of TM (mol)}]×100 Total amount of each compound (mol)=HPLC area value (mAU) of each compound/HPLC area value (mAU/mol) per mol of each compound

Workup

  1. additionAfter adding compounds
  2. customsealed air-tight
  3. customAfter the completion of the reaction
  4. customCalculation of the yield from the HPLC area % of the subject material
  5. customYield (%) of TM=total amount of TM (mol)/[{total amount of A (mol)+total amount of C (mol)×2+total amount of TM (mol)

Sources & evidence

ORD record
ord-a0c59cec13d5466e9c97bfcb653b796e
Source dataset
uspto-grants-2014_12
Patent number
US08916714B2

Reaction notes

Loading…