Tetrahydrofuran → (S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione

HRID 853847Notes

Reaction equation

HRID 853847 reaction equation
[O:1]=[C:2]1[C:10](=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12](Cl)(=[O:14])=[O:13])[CH:8]=2)[NH:3]1.C1COCC1.[O:21]([CH2:28][C@@H:29]1[CH2:33][CH2:32][CH2:31][NH:30]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)C(C)C)(C)C>C(Cl)(Cl)Cl>[O:21]([CH2:28][C@@H:29]1[CH2:33][CH2:32][CH2:31][N:30]1[S:12]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[C:10]2=[O:11])(=[O:14])=[O:13])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9855629(2S)-2-(phenoxymethyl)pyrrolidineHCID 159089472,3-Dioxoindoline-5-sulfonyl chloride

Product 1

HCID 9821545(S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dioneYield 88.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a cold solution of 2,3-dioxo-2,3-dihydro-1-H-indole-5-sulfonylchloride (3.80 g, 15.5 mmol ) in a 1:1 mixture of THF:CHCl3 (194 mL) was added drop-wise via syringe pump a solution of (2S)-2-(phenoxymethyl)pyrrolidine (2.85 g, 16.1 mmol, 1.03 eq) (J. Med. Chem, 44, 2014, 2001) and N,N-diisopropylethylamine (5.61 mL, 32.2 mmol, 2 eq) in CHCl3 (30 mL) over a period of 50 minutes under a dry N2 atmosphere with cooling in an ice bath. After stirring at room temperature for 64 hr the reaction mixture was concentrated and the crude product was flash chromatographed twice using Biotage KP silica gel, and gradient of 98/2 CH2Cl2/CH3OH as eluent on the first column and 90/10 CH2Cl2/CH3OH as eluent on the second column to give the title compound as a dark green solid (5.29 g, 88% yield). NMR (400 MHz, DMSO-d6): consistent. MS: (ES−) m/z 385 [M−H]. MS: (ES+) m/z 387 [M+H].

Workup

  1. customof 50 minutes
  2. temperaturewith cooling in an ice bath
  3. concentrationwas concentrated
  4. customchromatographed twice

Sources & evidence

ORD record
ord-eda36d594b914af085a29acca5e37383
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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