Piperazine → HCID 178486248, compound

HRID 736268Notes

Reaction equation

HRID 736268 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[CH2:8][C:9]1[CH:43]=[CH:42][C:12]([C:13]([NH:15][C:16]2[C:17]3[CH:30]=[C:29]([C:31]([NH:33][N:34]([CH3:41])[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:32])[S:28][C:18]=3[N:19](C(OC(C)(C)C)=O)[N:20]=2)=[O:14])=[CH:11][CH:10]=1.ClCC1C=CC(C(NC2C3C=C(C(NN(C4C=CC(Cl)=CC=4)C)=O)SC=3N(C(OC(C)(C)C)=O)N=2)=O)=CC=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:41][N:34]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[NH:33][C:31]([C:29]1[S:28][C:18]2[NH:19][N:20]=[C:16]([NH:15][C:13](=[O:14])[C:12]3[CH:42]=[CH:43][C:9]([CH2:8][N:1]4[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]4)=[CH:10][CH:11]=3)[C:17]=2[CH:30]=1)=[O:32]

Participants

6

Reactant 3

HCID 4837PiperazineHCID 57848822HCID 57848822, compoundHCID 57848870HCID 57848870, compound

Product 1

HCID 178486248HCID 178486248, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

27 mg (74 μmol) of tetrabutylammonium iodide, followed by 96 mg (1.11 mmol) of piperazine, are added to a solution of 200 mg (0.37 mmol) of an approximately 70:30 mixture of tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate and tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl)-thieno[2,3-c]pyrazole-1-carboxylate in 6 mL of dimethylformamide under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 16 hours, and then treated with ice. It is then extracted with ethyl acetate and then twice with dichloromethane. The organic extracts are combined and then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is dissolved in 3 mL of methanol and the solution is introduced into a microwave oven tube. The tube is stoppered and the reaction mixture is irradiated at a temperature in the region of 100° C. for twice 30 minutes. The reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is purified by preparative LC/MS (conditions B). 83 mg of N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]-4-piperazin-1-ylmethylbenzamide are thus obtained in the form of a yellow powder melting at 176° C. LC-MS-DAD-ELSD: 490(+)=M(+H)(+).

Workup

  1. additiontreated with ice
  2. extractionIt is then extracted with ethyl acetate
  3. concentrationconcentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
  4. dissolutionThe residue is dissolved in 3 mL of methanol
  5. additionthe solution is introduced into a microwave oven tube
  6. customthe reaction mixture is irradiated at a temperature in the region of 100° C. for twice 30 minutes
  7. concentrationThe reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
  8. customThe residue is purified by preparative LC/MS (conditions B)

Sources & evidence

ORD record
ord-8583553c88b843c9bef00e9cf47332a3
Source dataset
uspto-grants-2009_09
Patent number
US07595320B2

Reaction notes

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