Pyrrolidine → 1-Benzenesulfonyl-7-fluoro-3-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-indole

HRID 644073Notes

Reaction equation

HRID 644073 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[F:19])[C:12]([C:20]3[S:24][C:23]([CH:25]=O)=[CH:22][CH:21]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.C([BH3-])#N.[Na+]>C(O)(=O)C>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[F:19])[C:12]([C:20]3[S:24][C:23]([CH2:25][N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:22][CH:21]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 860732925-(1-Benzenesulfonyl-7-fluoroindol-3-yl)-thiophene-2-carboxaldehyde

Product 1

HCID 686951601-Benzenesulfonyl-7-fluoro-3-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-indole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidCatalyst

Procedure

To the crude 5-(1-benzenesulfonyl-7-fluoroindol-3-yl)-thiophene-2-carboxaldehyde was sequentially added 4 Å molecular sieves (1 g), pyrrolidine (0.44 ml, 5.36 mmol), sodium cyanoborohydride (0.034 g, 0.54 mmol) and glacial acetic acid (1 drop). The resulting mixture was then stirred at room temperature for 18 h, filtered and the filter cake washed with methanol (2×30 ml) and dichloromethane (2×30 ml). The combined filtrate was concentrated in vacuo, dissolved in dichloromethane (20 ml), washed with aqueous sodium hydroxide (2M; 15 ml), dried with sodium sulphate and concentrated in vacuo. The residue was then purified by flash column chromatography eluting with 0-10% (v/v) methanol in dichloromethane to afford 1-benzenesulfonyl-7-fluoro-3-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-indole as a yellow oil (0.22 g, 0.46 mmol).

Workup

  1. filtrationfiltered
  2. washthe filter cake washed with methanol (2×30 ml) and dichloromethane (2×30 ml)
  3. concentrationThe combined filtrate was concentrated in vacuo
  4. dissolutiondissolved in dichloromethane (20 ml)
  5. washwashed with aqueous sodium hydroxide (2M; 15 ml)
  6. dry with materialdried with sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue was then purified by flash column chromatography
  9. washeluting with 0-10% (v/v) methanol in dichloromethane

Sources & evidence

ORD record
ord-108b4a2fa0f04bbfb94853844b5959f3
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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