1-Methylpiperazine → 3-{3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]benzyl}-5-trifluoromethyl-3H-benzothiazol-2-one

HRID 330806Notes

Reaction equation

HRID 330806 reaction equation
I[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:9]=[C:10]([CH:26]=[CH:27][CH:28]=2)[CH2:11][N:12]2[C:16]3[CH:17]=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=[CH:20][C:15]=3[S:14][C:13]2=[O:25])=[N:6][CH:7]=1.[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.O>[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([C:2]2[CH:3]=[N:4][C:5]([C:8]3[CH:9]=[C:10]([CH:26]=[CH:27][CH:28]=3)[CH2:11][N:12]3[C:16]4[CH:17]=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=[CH:20][C:15]=4[S:14][C:13]3=[O:25])=[N:6][CH:7]=2)[CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 531671-MethylpiperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl2×HCID 18407952Tripotassium phosphate trihydrateHCID 584963413-[3-(5-iodopyrimidin-2-yl)benzyl]-5-trifluoromethyl-3H-benzothiazol-2-one

Product 1

HCID 468467263-{3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]benzyl}-5-trifluoromethyl-3H-benzothiazol-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

513 mg (1 mmol) of 3-[3-(5-iodopyrimidin-2-yl)benzyl]-5-trifluoromethyl-3H-benzothiazol-2-one is suspended in toluene, briefly heated to 100° C. and cooled to room temperature. 134 μl (1.2 mmol) of methylpiperazine, 297 mg (1.4 mmol) of potassium phosphate trihydrate, and 33 mg (0.08 mmol) of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl and 18 mg (0.02 mmol) of tris(benzylideneacetone)dipalladium are subsequently added and stirred at 100° C. under an argon atmosphere. 33 mg (0.08 mmol) of 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl and 18 mg (0.02 mmol) of tris(benzylideneacetone)dipalladium are subsequently again added and stirred at 100° C. for a further 24 h under an argon atmosphere. Water is added to the reaction mixture, which is then extracted with ethyl acetate and dried. The crude product is purified by means of preparative HPLC. The product is in the form of the trifluoroacetate.

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred at 100° C. for a further 24 h under an argon atmosphere
  3. extractionis then extracted with ethyl acetate
  4. customdried
  5. customThe crude product is purified by means of preparative HPLC

Sources & evidence

ORD record
ord-15da7088dc4548dc898013bf70f4bbf6
Source dataset
uspto-grants-2014_11
Patent number
US08877751B2

Reaction notes

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