Thionyl Chloride → 2-Chloro-N-{2-[4-(4-Methyl-Piperazine-1-Carbonyl)-Phenylamino]-Pyrimidin-5-yl}-5-(3-Trifluoromethyl-Benzoylamino)-Benzamide

HRID 1662837Notes

Reaction equation

HRID 1662837 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:18])=[C:13]([CH:17]=1)[C:14](O)=[O:15])=[O:7].S(Cl)(Cl)=O.[NH2:28][C:29]1[CH:30]=[N:31][C:32]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]([N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[O:43])=[CH:38][CH:37]=2)=[N:33][CH:34]=1>ClCCl.C1COCC1>[Cl:18][C:12]1[CH:11]=[CH:10][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:19]=[CH:20][CH:21]=[C:3]([C:2]([F:1])([F:22])[F:23])[CH:4]=2)=[CH:17][C:13]=1[C:14]([NH:28][C:29]1[CH:34]=[N:33][C:32]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]([N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[O:43])=[CH:38][CH:37]=2)=[N:31][CH:30]=1)=[O:15]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 534011722-Chloro-5-(3-(trifluoromethyl)benzamido)benzoic acidHCID 58748687(4-(5-Aminopyrimidin-2-ylamino)phenyl)(4-methylpiperazin-1-yl)methanone

Product 1

HCID 249621872-Chloro-N-{2-[4-(4-Methyl-Piperazine-1-Carbonyl)-Phenylamino]-Pyrimidin-5-yl}-5-(3-Trifluoromethyl-Benzoylamino)-BenzamideYield 52%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of intermediate 1 (Example 2) (40 mg, 1.2 mmol) and thionyl chloride (875 μL, 12 mmol) in dichloromethane (20 mL) was heated under reflux for 6 h. The reaction mixture was evaporated to dryness. To the residue was added (4-(5-aminopyrimidin-2-ylamino)phenyl)(4-methylpiperazin-1-yl)methanone (20 mg, 0.064 mmol) and TEA (44 μL, 0.31 mmol) in THF (7 mL). The reaction mixture was stirred at room temperature for 1 h and evaporated. The residue was purified by HPLC to give title compound as a yellow solid (21 mg, 52%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 6 h
  3. customThe reaction mixture was evaporated to dryness
  4. customevaporated
  5. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-c8b262fff9164d8eadebfd8049e4f223
Source dataset
uspto-grants-2011_10
Patent number
US08030487B2

Reaction notes

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