Azetidine → HCID 178486244, compound

HRID 736273Notes

Reaction equation

HRID 736273 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.Cl[CH2:6][C:7]1[CH:41]=[CH:40][C:10]([C:11]([NH:13][C:14]2[C:15]3[CH:28]=[C:27]([C:29]([NH:31][N:32]([CH3:39])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:30])[S:26][C:16]=3[N:17](C(OC(C)(C)C)=O)[N:18]=2)=[O:12])=[CH:9][CH:8]=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>[N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:11]([NH:13][C:14]3[C:15]4[CH:28]=[C:27]([C:29]([NH:31][N:32]([CH3:39])[C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=5)=[O:30])[S:26][C:16]=4[NH:17][N:18]=3)=[O:12])=[CH:40][CH:41]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10422AzetidineHCID 57848822HCID 57848822, compoundHCID 57848870HCID 57848870, compound

Product 1

HCID 178486244HCID 178486244, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

27 mg (74 μmol) of tetrabutylammonium iodide and then 75 μL (1.11 mmol) of azetidine 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). 3 mg of 4-azetidin-1-ylmethyl-N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]benzamide are thus obtained in the form of a yellow powder melting from 155 to 160° C. LC-MS-DAD-ELSD: 461(+)=(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-620bbb88d90b4952a17ea89fbda0521d
Source dataset
uspto-grants-2009_09
Patent number
US07595320B2

Reaction notes

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