Hydrochloric Acid → 2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

HRID 2283516Notes

Reaction equation

HRID 2283516 reaction equation
[NH2-].[Na+].Cl[C:4]1[CH:9]=[C:8]([Cl:10])[N:7]=[C:6]([CH3:11])[N:5]=1.[NH2:12][C:13]1[S:14][C:15]([C:18]([NH:20][C:21]2[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:28])=[O:19])=[CH:16][N:17]=1.Cl>O.C1COCC1>[Cl:10][C:8]1[N:7]=[C:6]([CH3:11])[N:5]=[C:4]([NH:12][C:13]2[S:14][C:15]([C:18]([NH:20][C:21]3[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:28])=[O:19])=[CH:16][N:17]=2)[CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24533Sodium amideHCID 2349974,6-Dichloro-2-methylpyrimidineHCID 219116442-Amino-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

Product 1

HCID 112694102-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
7.5 °C

Procedure

Into a RBF 6.6 g of Sodium Amide was added at 30-35° C. under N2 atmosphere and stirring was done for 10-15 minutes. Then the reaction mass was cooled to 5-10° C. and 120.0 mL THF and 7.92 g 4,6-Dichloro-2-methyl pyrimidine were added to the reaction mass. Addition of 10.0 g 2-amino-N-(2-chloro-6-methyl phenyl)-5-thiazole carboxamide was then performed into the reaction mass. The reaction mass was stirred for ˜40 mins at 30-35° C. to get clear solution which was transferred to an addition dropper. At temperature of 5-10° C., the reaction mass was slowly added over 30 minutes, into another RBF having 40.0 mL THF. At the same temperature, the reaction mass was stirred for 1.0-1.5 hrs. Then the reaction mass temperature was increased to 30-35° C., where stirring was performed for 3 to 4 hrs. On completion of the reaction as verified by TLC, the reaction mass was cooled slowly to a temperature of 0-5° C. Then the reaction mass pH was adjusted to 3-4 by addition of 22.4 mL HCl and 240 mL water over 10-15 mins. The reaction mass was then stirred for 2.0-2.5 hrs at 0-5° C.

Workup

  1. stirringThe reaction mass was stirred for ˜40 mins at 30-35° C.
  2. customto get clear solution which
  3. additionAt temperature of 5-10° C., the reaction mass was slowly added over 30 minutes, into another RBF
  4. stirringAt the same temperature, the reaction mass was stirred for 1.0-1.5 hrs
  5. temperatureThen the reaction mass temperature was increased to 30-35° C.
  6. stirringwhere stirring
  7. waitwas performed for 3 to 4 hrs
  8. customOn completion of the reaction
  9. temperaturethe reaction mass was cooled slowly to a temperature of 0-5° C
  10. stirringThe reaction mass was then stirred for 2.0-2.5 hrs at 0-5° C.

Sources & evidence

ORD record
ord-b90ed8aea22a423f85c05da82e1165cb
Source dataset
uspto-grants-2015_09
Patent number
US09145406B2

Reaction notes

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