2-Chloro-6-methylaniline → 2-(6-bromo-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-formamide

HRID 515258Notes

Reaction equation

HRID 515258 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[S:11][C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=2)[CH:3]=1.CCOC(C1(C(OCC)=O)NC(=O)CC1C1C=CC=CC=1)=O.[Cl:40][C:41]1[CH:47]=[CH:46][CH:45]=[C:44]([CH3:48])[C:42]=1[NH2:43].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[S:11][C:12]([C:15]([NH:43][C:42]3[C:44]([CH3:48])=[CH:45][CH:46]=[CH:47][C:41]=3[Cl:40])=[O:17])=[CH:13][N:14]=2)[CH:3]=1

Participants

7

Reactant 5

HCID 68972-Chloro-6-methylaniline2×HCID 8471TriethylamineHCID 986274-Phenyl-5,5-dicarbethoxy-2-pyrrolidinoneHCID 516892Sodium BicarbonateHCID 498218842-(6-Bromo-2-methylpyrimidin-4-ylamino)thiazole-5-formic acid2×

Product 1

HCID 866764302-(6-bromo-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-formamideYield 77.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen atmosphere, 2-(6-bromo-2-methylpyrimidin-4-ylamino)thiazole-5-formic acid (Compound 12) (15.8 g, 0.05 mol), PDCP (9.0 mL, 0.06 mol) and 2-chloro-6-methylaniline (Compound 8)) (7.4 mL, 0.06 mol) were added into methylene dichloride (650 mL) by stirring and cooling, and then triethylamine (20.4 mL, 0.15 mol) was added by droplets at 0° C. When finish adding, it reacted by stirring at room temperature overnight. Saturated sodium bicarbonate aqueous solution was added and stirred for 15 mins and then filtrated. The cake was taken up and added in DMSO (80 mL) and heated to 60° C.-70° C. when stirring. After dissolving, the mixture of water and ethanol (1:1, 320 mL) was added in thermal insulation. Crystals precipitated by stirring and then cooled down to 0° C. to grow the grain for 1 h. After air pump filtration the cake was rinsed by water and then by the mixture of water and ethanol (1:1), and dried by air pump. With phosphorus pentoxide as an auxiliary desiccant, the cake was dried by vacuum (−0.095 MPa) at about 50° C. to give Compound 14 (17.0 g, yield: 77.5%).

Workup

  1. temperaturecooling
  2. additionWhen finish adding
  3. customit reacted
  4. stirringby stirring at room temperature overnight
  5. stirringstirred for 15 mins
  6. filtrationfiltrated
  7. additionadded in DMSO (80 mL)
  8. temperatureheated to 60° C.-70° C. when
  9. stirringstirring
  10. dissolutionAfter dissolving
  11. additionthe mixture of water and ethanol (1:1, 320 mL)
  12. additionwas added in thermal insulation
  13. customCrystals precipitated
  14. stirringby stirring
  15. customfor 1 h
  16. filtrationAfter air pump filtration the cake
  17. washwas rinsed by water
  18. additionby the mixture of water and ethanol (1:1)
  19. customdried by air pump
  20. dry with materialWith phosphorus pentoxide as an auxiliary desiccant, the cake was dried by vacuum (−0.095 MPa) at about 50° C.

Sources & evidence

ORD record
ord-27302e4f1d534f119de628223f62b7fd
Source dataset
uspto-grants-2015_08
Patent number
US09108954B2

Reaction notes

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