Methanesulfonyl chloride → HCID 69883429, compound

HRID 397851Notes

Reaction equation

HRID 397851 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:10]3[C:11]4[C:36](=[O:37])[NH:35][C:34](=[O:38])[C:12]=4[C:13]4[C:14]5[C:19]([N:20]([C@@H:22]6[O:30][C@H:29]([CH2:31][OH:32])[C@@H:27]([OH:28])[C@H:25](O)[C@H:23]6[OH:24])[C:21]=4[C:9]=3[NH:8][C:6]=2[CH:7]=1)=[CH:18][C:17]([F:33])=[CH:16][CH:15]=5.CS(Cl)(=O)=O>N1C=CC=CC=1>[C@@H:22]1([N:20]2[C:21]3[C:9]4[NH:8][C:6]5[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=5[C:10]=4[C:11]4[C:36](=[O:37])[NH:35][C:34](=[O:38])[C:12]=4[C:13]=3[C:14]3[C:19]2=[CH:18][C:17]([F:33])=[CH:16][CH:15]=3)[O:30][C@@H:29]2[CH2:31][O:32][C@@H:25]([C@@H:27]2[OH:28])[C@H:23]1[OH:24]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 9892980HCID 9892980, compound

Product 1

HCID 69883429HCID 69883429, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

2,10-Difluoro-12,13-dihydro-12-[β-D-glucopyranosyl]-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (1.0 g, 1.91 mmol) was dissolved in dry pyridine under nitrogen at room temperature and treated with flame-dried, powdered 4A molecular sieves (0.60 g). The mixture. was cooled to −20° C. for 15 min before methanesulfonyl chloride (0.26 mL, 3.34 mmol, 1.75 eq.) was added neat. The flask was sealed and stored at 0° C. for 6 h prior to concentration in vacuo. Purification of the residue by flash chromatography on silica gel (elution with tetrahydrofuran/dichloromethane/methanol, 68:30:2) gave an enriched fraction (280 mg, 24%) containing the title compound as well as a small amount of other closely-spaced by-products which was carried on directly. Potassium phthalimide (0.45 g, 2.43 mmol) was added in one portion to a stirred solution of 2,10-difluoro-12,13-dihydro-12-[6—O-(methylsulfonyl)-β-D-glucopyranosyl]-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (200 mg, 0.33 mmol) in anhydrous dimethylformamide (10 mL) before the mixture was heated to 130° C. for 3 h, cooled to ambient temperature, and concentrated down in vacuo overnight. The residue was then taken up in ethyl acetate (some tetrahydrofuran was added) and washed with 0.1N hydrochloric acid and brine. Following drying and solvent concentration, the residue was purified by flash chromatography on silica gel (elution with 7% methanol in chloroform) to yield 2,10-difluoro-12,13-dihydro-12-[6-deoxy-6-(phthalimido)-β-D-glucopyranosyl]-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (46 mg, 21%) as a yellow solid as well as the title compound (22 mg, 13%, 2 steps) also as a yellow solid.

Workup

  1. additiontreated
  2. customwith flame-dried
  3. additionwas added neat
  4. customThe flask was sealed
  5. concentrationto concentration in vacuo
  6. customPurification of the residue by flash chromatography on silica gel (elution with tetrahydrofuran/dichloromethane/methanol, 68:30:2)
  7. customgave an enriched fraction (280 mg, 24%)

Sources & evidence

ORD record
ord-8da0ea01a3d14a8488ef59210c034379
Source dataset
uspto-grants-2003_08
Patent number
US06610727B2

Reaction notes

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