Dimethylformamide → ethyl 2-(3-cyano-2-cyclopentyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

HRID 1189538Notes

Reaction equation

HRID 1189538 reaction equation
[CH:1]1([C:6]2[N:10]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:9]([CH3:17])=[C:8]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[S:25]([N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)(=[O:27])=[O:26])[CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.ClS([N:37]=[C:38]=O)(=O)=O.CN(C)C=O>C(#N)C>[C:38]([C:7]1[C:8]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[S:25]([N:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)(=[O:26])=[O:27])=[C:9]([CH3:17])[N:10]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:6]=1[CH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1)#[N:37]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 53246982ethyl 2-(5-cyclopentyl-2-methyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

Product 1

HCID 53246146ethyl 2-(3-cyano-2-cyclopentyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of ethyl 2-(5-cyclopentyl-2-methyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (2.54 g, 5.54 mmol) in acetonitrile (28 mL) was added chlorosulfonyl isocyanate (0.818 ml, 9.42 mmol). The reaction was stirred at room temperature for 30 minutes, after which the starting pyrrole had still not been consumed. The reaction was then heated to 55° C. for 30 minutes after which the starting pyrrole was consumed (by LCMS analysis). To the reaction mixture at 55° C. was added N,N-dimethylformamide (0.729 ml, 9.42 mmol). The reaction was stirred at 55° C. for 30 minutes after which analysis of the reaction (by LCMS) indicated that the reaction to afford the desired product was complete. The reaction was quenched by the addition of water, and extracted with dichloromethane (3×50 mL), dried (sodium sulfate), filtered and concentrated to a deep maroon residue. Purification was achieved by silica gel chromatography (Luknova 240 g, 20 mL/min) using 1 to 7% of a 7:1 acetonitrile/methanol solution in dichloromethane over 70 minutes. The product ethyl 2-(3-cyano-2-cyclopentyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (747 mg, 1.55 mmol, 28% yield) was isolated as a white foam. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.01 (d, 1H), 7.40 (dd, 1H), 7.30 (ddd, 1H), 6.99 (d, 1H), 4.59 (s, 2H), 4.30 (s, 2H), 4.27 (q, 2H), 3.32-3.36 (m, 4H), 2.96 (m, 1H), 1.84-2.09 (m, 13H, composite of multiple shifts), 1.63-1.71 (m, 2H).

Workup

  1. customafter which the starting pyrrole had still not been consumed
  2. temperatureThe reaction was then heated to 55° C. for 30 minutes after which the starting pyrrole
  3. customwas consumed (by LCMS analysis)
  4. stirringThe reaction was stirred at 55° C. for 30 minutes
  5. customafter which analysis of the reaction (by LCMS)
  6. customindicated that the reaction

Sources & evidence

ORD record
ord-e1b71d084d954e3b8b054b8e0ba18cf8
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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