Benzenesulfonyl chloride → (3'S)-1'-(4-{[1-(Phenylsulfonyl)-1H-benzimidazol-2-yl]methyl}-benzoyl)-1,3'-bipyrrolidine Fumarate

HRID 1163093Notes

Reaction equation

HRID 1163093 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([C:15]([N:17]2[CH2:21][CH2:20][C@H:19]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH2:18]2)=[O:16])=[CH:13][CH:12]=1.C(N(CC)CC)C.[C:36]1([S:42](Cl)(=[O:44])=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50]>ClCCl.ClCCl.CO>[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]/[C:49]([OH:51])=[O:50].[C:36]1([S:42]([N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[C:2]2[CH2:10][C:11]2[CH:28]=[CH:27][C:14]([C:15]([N:17]3[CH2:21][CH2:20][C@H:19]([N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:18]3)=[O:16])=[CH:13][CH:12]=2)(=[O:44])=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 444972Fumaric AcidHCID 58970760(3'S)-1'-[4-(1H-Benzimidazol-2-ylmethyl)benzoyl]-1,3'-bipyrrolidine

Product 1

HCID 68427731(3'S)-1'-(4-{[1-(Phenylsulfonyl)-1H-benzimidazol-2-yl]methyl}-benzoyl)-1,3'-bipyrrolidine Fumarate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (3′S)-1′-[4-(1H-benzimidazol-2-ylmethyl)benzoyl]-1,3′-bipyrrolidine (100 mg, 0.267 mmol) in anhydrous dichloromethane was cooled to 0° C. under an inert atmosphere, treated with triethylamine (TEA) (32 mg, 0.32 mmol) followed by dropwise addition of a solution of benzenesulfonyl chloride (51.7 mg, 0.293 mmol) in anhydrous dichloromethane, stirred at 0° C. for 1 h, warmed to room temperature for 1 h and concentrated under reduced pressure. The resultant residue was partitioned between dichloromethane and 5% aqueous NaHCO3. The organic phase was separated, washed with water, dried over sodium sulfate and concentrated under reduced pressure to give a residue. This residue was treated with fumaric acid in dichloromethane/methanol to afford the title compound, 1H NMR (300 MHz, DMSO-d6, +TFA): 7.96 (d, 1 H), 7.90 (d, 2 H), 7.78-7.66 (m, 2 H), 7.59 (m, 2 H), 7.49 (d, 2 H), 7.45-7.29 (m, 4 H), 6.63 (s, 2 H), 4.67 (s, 2 H), 3.58-3.41 (m, 4 H), 3.10-2.76 (m, 5 H), 2.19 (m, 1 H), 2.00 (m, 1 H), 1.91-1.73 (m, 4 H). [M+H] 515.1

Workup

  1. temperaturewarmed to room temperature for 1 h
  2. concentrationconcentrated under reduced pressure
  3. customThe resultant residue was partitioned between dichloromethane and 5% aqueous NaHCO3
  4. customThe organic phase was separated
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue

Sources & evidence

ORD record
ord-25d1edf6f37240f8bf74b0ed36784b64
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

Loading…