4-Toluenesulfonyl chloride → HCID 131735585, compound

HRID 525296Notes

Reaction equation

HRID 525296 reaction equation
[C:1]([O:5][C:6](=[O:31])[N:7]([C@H:9]([C:11](=[O:30])[NH:12][C@H:13]([C:17]([N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][CH:20]1[CH2:28][OH:29])=[O:18])[CH:14]([CH3:16])[CH3:15])[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[S:39](Cl)([C:42]1[CH:48]=[CH:47][C:45]([CH3:46])=[CH:44][CH:43]=1)(=[O:41])=[O:40]>C(Cl)Cl>[C:1]([O:5][C:6]([N:7]([CH3:8])[C@@H:9]([CH3:10])[C:11]([NH:12][C@@H:13]([CH:14]([CH3:16])[CH3:15])[C:17]([N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][C@H:20]1[CH2:28][O:29][S:39]([C:42]1[CH:48]=[CH:47][C:45]([CH3:46])=[CH:44][CH:43]=1)(=[O:41])=[O:40])=[O:18])=[O:30])=[O:31])([CH3:2])([CH3:4])[CH3:3].[C:1]([O:5][C:6]([N:7]([CH3:8])[C@@H:9]([CH3:10])[C:11]([NH:12][C@@H:13]([CH:14]([CH3:16])[CH3:15])[C:17]([N:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH2:21][C@@H:20]1[CH2:28][O:29][S:39]([C:42]1[CH:48]=[CH:47][C:45]([CH3:46])=[CH:44][CH:43]=1)(=[O:41])=[O:40])=[O:18])=[O:30])=[O:31])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 117869999HCID 117869999, compound

Product 2

HCID 131735585HCID 131735585, compoundHCID 131735586HCID 131735586, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {(S)-1-[(S)-1-(2-hydroxymethyl-2,3-dihydro-pyrrolo[2,3-b]pyridine-1-carbonyl)-2-methyl-propylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (4.5 g, 10.36 mmol) in DCM (150 mL), was added triethylamine (4.25 mL, 31.106 mmol) followed by the slow addition of tosyl chloride (3.0 g, 15.55 mmol) at 0° C. The reaction mixture was stirred at rt for 16 hand then the reaction mixture was concentrated in vacuo. Water was added to the residue and the resulting mixture was extracted with EtOAc (300 mL×2). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica gel, 18% EtOAc in hexanes) to give toluene-4-sulfonic acid (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-2-ylmethyl ester (2.7 g) and toluene-4-sulfonic acid (R)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-2-ylmethyl ester (1 g), m/z=589 (M+H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additionWater was added to the residue
  3. extractionthe resulting mixture was extracted with EtOAc (300 mL×2)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash chromatography (silica gel, 18% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a5e84868c8094028bc60636ae4b15ac5
Source dataset
uspto-grants-2016_05
Patent number
US09340573B2

Reaction notes

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