Dimethylformamide → (R)-3-(N-Benzyloxycarbonylpyrrolidin-2-ylmethyl)-7-bromo-5-(methylaminosulfonylmethyl)-1H-indole

HRID 1077871Notes

Reaction equation

HRID 1077871 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH:16]=[CH:17][CH2:18][N:19]([C:26]1[C:31](Br)=[CH:30][C:29]([CH2:33][S:34]([NH:37][CH3:38])(=[O:36])=[O:35])=[CH:28][C:27]=1[Br:39])C(=O)C(F)(F)F)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C=O>C(N(CC)CC)C.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@@H:12]1[CH2:16][C:17]1[C:31]2[C:26](=[C:27]([Br:39])[CH:28]=[C:29]([CH2:33][S:34]([NH:37][CH3:38])(=[O:35])=[O:36])[CH:30]=2)[NH:19][CH:18]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 53700037(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-[N-(4-methylaminosulfonylmethyl-2,6-dibromophenyl)-N-trifluoroacetylamino]propene

Product 1

HCID 11038630(R)-3-(N-Benzyloxycarbonylpyrrolidin-2-ylmethyl)-7-bromo-5-(methylaminosulfonylmethyl)-1H-indole

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-[N-(4-methylaminosulfonylmethyl-2,6-dibromophenyl)-N-trifluoroacetylamino]propene (9.00 g) in triethylamine (70 mL) containing N,N-dimethylformamide (20 mL), tetra-n-butylammonium chloride (3.61 g) and palladium acetate (1.01 g) was heated at 80° C. until conversion was complete. The cooled reaction mixture was filtered through CELITE and washed with methylene chloride. The combined filtrate and washings were then evaporated in vacuo onto silica gel (15 g) then purified by column chromatography (SiO2-1.6 kg) eluted with 4% acetone in chloroform. The product-rich fractions were combined and evaporated then re-purified by crystallisation from a mixture of diethyl ether (50 mL) and methylene chloride (10 mL). The title compound was recovered by filtration (washing with hexanes) as a colorless solid (2.40 g). TLC (methylene chloride/acetone 10:1) Rf=0.35; Anal calcd. for C23H26BrN3O4S: C, 53.1; H, 5.0; N, 8.1. Found C, 53.13; H, 5.0; N, 7.8.

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through CELITE
  3. washwashed with methylene chloride
  4. customThe combined filtrate and washings were then evaporated in vacuo onto silica gel (15 g)
  5. customthen purified by column chromatography (SiO2-1.6 kg)
  6. washeluted with 4% acetone in chloroform
  7. customevaporated
  8. customthen re-purified by crystallisation from a mixture of diethyl ether (50 mL) and methylene chloride (10 mL)
  9. filtrationThe title compound was recovered by filtration (washing with hexanes) as a colorless solid (2.40 g)

Sources & evidence

ORD record
ord-492c276220fe4318a268a12af99194da
Source dataset
uspto-grants-1996_08
Patent number
US05545644

Reaction notes

Loading…