Pyrrolidine → n-[5-(n'-Methyl-n'-phenylhydrazinocarbonyl)-1h-thieno[2,3-c]pyrazol-3-yl]-4-pyrrolidin-1-ylmethylbenzamide

HRID 736272Notes

Reaction equation

HRID 736272 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:7][C:8]1[CH:42]=[CH:41][C:11]([C:12]([NH:14][C:15]2[C:16]3[CH:29]=[C:28]([C:30]([NH:32][N:33]([CH3:40])[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)=[O:31])[S:27][C:17]=3[N:18](C(OC(C)(C)C)=O)[N:19]=2)=[O:13])=[CH:10][CH:9]=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>[CH3:40][N:33]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH:32][C:30]([C:28]1[S:27][C:17]2[NH:18][N:19]=[C:15]([NH:14][C:12](=[O:13])[C:11]3[CH:41]=[CH:42][C:8]([CH2:7][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:9][CH:10]=3)[C:16]=2[CH:29]=1)=[O:31]

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 57848822HCID 57848822, compoundHCID 57848870HCID 57848870, compound

Product 1

HCID 178486245n-[5-(n'-Methyl-n'-phenylhydrazinocarbonyl)-1h-thieno[2,3-c]pyrazol-3-yl]-4-pyrrolidin-1-ylmethylbenzamide

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

27 mg (74 μmol) of tetrabutylammonium iodide and then 93 μL (1.11 mmol) of pyrrolidine 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 poured onto ice. It is then extracted twice with a 50/50 mixture of ethyl acetate and heptane. The organic extracts are combined, dried over magnesium sulfate and then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is dissolved in 4 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 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). 25 mg of N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]-4-pyrrolidin-1-ylmethylbenzamide are thus obtained in the form of a yellow powder melting from 172 to 178° C. LC-MS-DAD-ELSD: 475(+)=(M+H)(+).

Workup

  1. additionpoured onto ice
  2. extractionIt is then extracted twice with a 50/50 mixture of ethyl acetate and heptane
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
  5. dissolutionThe residue is dissolved in 4 mL of methanol
  6. additionthe solution is introduced into a microwave oven tube
  7. customthe reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes
  8. concentrationThe reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
  9. customThe residue is purified by preparative LC/MS (conditions B)

Sources & evidence

ORD record
ord-16ff9aa3641341209659616ed69d12c5
Source dataset
uspto-grants-2009_09
Patent number
US07595320B2

Reaction notes

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