Cyclobutanecarbonyl chloride → HCID 57703885, compound

HRID 1472216Notes

Reaction equation

HRID 1472216 reaction equation
C(OC([N:6]1[C:10]([NH:11][C:12](=[O:27])[C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[CH:15][C:14]=2[NH2:26])=[C:9]2[CH2:28][N:29]([S:33]([C:36]3[CH:41]=[C:40]([F:42])[CH:39]=[C:38]([F:43])[CH:37]=3)(=[O:35])=[O:34])[C:30]([CH3:32])([CH3:31])[C:8]2=[N:7]1)=O)C.[CH:44]1([C:48](Cl)=[O:49])[CH2:47][CH2:46][CH2:45]1>ClCCl.C(N(CC)C(C)C)(C)C>[CH:44]1([C:48]([NH:26][C:14]2[CH:15]=[C:16]([N:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)[CH:17]=[CH:18][C:13]=2[C:12]([NH:11][C:10]2[C:9]3[CH2:28][N:29]([S:33]([C:36]4[CH:37]=[C:38]([F:43])[CH:39]=[C:40]([F:42])[CH:41]=4)(=[O:34])=[O:35])[C:30]([CH3:32])([CH3:31])[C:8]=3[NH:7][N:6]=2)=[O:27])=[O:49])[CH2:47][CH2:46][CH2:45]1

Participants

5

Reactant 2

HCID 78705Cyclobutanecarbonyl chlorideHCID 57703873HCID 57703873, compound

Product 1

HCID 57703885HCID 57703885, compoundYield 19.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 3-[2-amino-4-(4-methyl-piperazin-1-yl)-benzoylamino]-5-(3,5-difluoro-benzenesulfonyl)-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester (105 mg, 0.17 mmol) in dichloromethane (5 mL) and N,N-diisopropylethylamine (1 mL), cyclobutanecarbonyl chloride (28.5 microL, 0.25 mmol) was added and the reaction mixture stirred at room temperature for 2 hours. The mixture was then diluted with dichloromethane (30 mL), washed with water (30 mL), dried over sodium sulphate and evaporated to dryness. The crude oil was then treated with MeOH (5 mL) and triethylamine (3 mL) and stirred at room temperature for 2 hours. The solvent was removed under vacuum and the residue purified by flash chromatography on silica gel, using a mixture dichloromethane-MeOH-30% NH4OH 100:10:1 as the eluant, affording the title compound as white solid (21 mg).

Workup

  1. washwashed with water (30 mL)
  2. dry with materialdried over sodium sulphate
  3. customevaporated to dryness
  4. additionThe crude oil was then treated with MeOH (5 mL) and triethylamine (3 mL)
  5. stirringstirred at room temperature for 2 hours
  6. customThe solvent was removed under vacuum
  7. customthe residue purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-aaef6e2eb37a4b609b6d4c750dafdce9
Source dataset
uspto-grants-2015_04
Patent number
US09012487B2

Reaction notes

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