Diisopropylethylamine → 5-(3,5-difluoro-benzenesulfonyl)-3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester

HRID 2427251Notes

Reaction equation

HRID 2427251 reaction equation
Cl.[CH2:2]([O:4][C:5]([N:7]1[C:11]([NH:12][C:13](=[O:32])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:10]2[CH2:33][NH:34][C:35]([CH3:37])([CH3:36])[C:9]2=[N:8]1)=[O:6])[CH3:3].C(N(CC)C(C)C)(C)C.[F:47][C:48]1[CH:49]=[C:50]([S:55](Cl)(=[O:57])=[O:56])[CH:51]=[C:52]([F:54])[CH:53]=1>ClCCl>[CH2:2]([O:4][C:5]([N:7]1[C:11]([NH:12][C:13](=[O:32])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:10]2[CH2:33][N:34]([S:55]([C:50]3[CH:49]=[C:48]([F:47])[CH:53]=[C:52]([F:54])[CH:51]=3)(=[O:57])=[O:56])[C:35]([CH3:36])([CH3:37])[C:9]2=[N:8]1)=[O:6])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740583,5-Difluorobenzenesulfonyl chlorideHCID 670102843-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester hydrochloride

Product 1

HCID 670087475-(3,5-difluoro-benzenesulfonyl)-3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-5,6-dihydro-4H-pyrrolo[3,4-c]pyrazole-2-carboxylic acid ethyl ester hydrochloride (1.24 g, 2.4 mmol) in dry dichloromethane (30 mL) was added N,N-diisopropylethylamine (1.67 mL, 9.6 mmol) and 3,5-difluorobenzenesulfonyl chloride (0.77 g, 3.6 mmol). After stirring at room temperature for 3 hours the mixture was diluted with dichloromethane (50 mL), washed with 1N HCl, water, saturated solution of NaHCO3, brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel eluting with ethyl acetate and then with dichloromethane/methanol 98:2 affording the title compound as white solid (1.4 g).

Workup

  1. washwashed with 1N HCl, water, saturated solution of NaHCO3, brine
  2. dry with materialdried over sodium sulfate
  3. customevaporated to dryness
  4. customThe crude was purified by flash chromatography on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-3073651504564136a455fa817874dcb5
Source dataset
uspto-grants-2011_06
Patent number
US07968583B2

Reaction notes

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