Tetrahydrofuran → HCID 67008776, compound

HRID 1256634Notes

Reaction equation

HRID 1256634 reaction equation
[CH2:1]([O:3][C:4]([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:5])[CH3:2].C(N(CC)C(C)C)(C)C.[N:53]1([C:59](Cl)=[O:60])[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1.O1CCCC1>O>[CH2:1]([O:3][C:4]([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[NH:26][C:59]([N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)=[O:60])=[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:5])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 57703873HCID 57703873, compound

Product 1

HCID 67008776HCID 67008776, compoundYield 30.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture 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 (308 mg, 0.5 mmol), N,N-diisopropylethylamine (0.104 mL, 0.6 mmol, 1.2 eq), morpholine-4-carbonyl chloride (1.2 mL, 10 mmol, 20 eq) and tetrahydrofuran (20 mL) was stirred at 60° C. for 7 days. The reaction mixture was then poured into water (100 mL), extracted with dichloromethane (100 mL), dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel (acetone as eluant) affording 112 mg of 5-(3,5-difluoro-benzenesulfonyl)-6,6-dimethyl-3-{4-(4-methyl-piperazin-1-yl)-2-[(morpholine-4-carbonyl)-amino]-benzoylamino}-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester that was treated with 10 mL of methanol/triethylamine 8:2 and stirred at room temperature overnight. The mixture was evaporated to dryness and the residue purified by flash chromatography on silica gel using dichloromethane-methanol-30% NH4OH 96:4:0.4 as eluant, yielding the title compound as white solid (50 mg).

Workup

  1. extractionextracted with dichloromethane (100 mL)
  2. dry with materialdried over sodium sulfate
  3. customevaporated to dryness
  4. customThe crude was purified by flash chromatography on silica gel (acetone as eluant)

Sources & evidence

ORD record
ord-5eacb3bb813e4bcf9ed91851aeb54c8a
Source dataset
uspto-grants-2013_06
Patent number
US08461193B2

Reaction notes

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