4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 2-(4-chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-hydroxy-2-hydroxymethyl-propyl ester

HRID 82249Notes

Reaction equation

HRID 82249 reaction equation
C(N(CC)CC)C.Cl.CN(C)C.[Cl:13][C:14]1[C:15]2[CH:22]=[CH:21][N:20]([C:23]([CH2:28][OH:29])([CH2:26][OH:27])[CH2:24][OH:25])[C:16]=2[N:17]=[CH:18][N:19]=1.[S:30](Cl)([C:33]1[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=1)(=[O:32])=[O:31]>ClCCl.O>[Cl:13][C:14]1[C:15]2[CH:22]=[CH:21][N:20]([C:23]([CH2:24][OH:25])([CH2:28][OH:29])[CH2:26][O:27][S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[C:16]=2[N:17]=[CH:18][N:19]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 10313079Trimethylamine HydrochlorideHCID 866721162-(4-Chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxymethyl-propane-1,3-diol

Product 1

HCID 86672115Toluene-4-sulfonic acid 2-(4-chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-hydroxy-2-hydroxymethyl-propyl esterYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.879 mL, 6.31 mmol) and trimethylamine hydrochloride (253 mg, 2.65 mmol) were added to a solution of 2-(4-chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxymethyl-propane-1,3-diol (Preparation 209, 650 mg, 2.52 mmol) in dichloromethane (20 mL) at 00° C. The mixture was treated portion-wise with tosyl chloride (505 mg, 2.65 mmol) and stirred at 00° C. for 16 hours. The reaction mixture was treated with water and stirred for 10 min. The resulting mixture was washed with citric acid, saturated aqueous sodium bicarbonate, and saturated brine, then evaporated in vacuo. The crude product was purified by column chromatography on silica gel (gradient of EtOAc:DCM 0:100 to 30:70) to afford the title compound as a colorless solid in 55% yield, 570 mg.

Workup

  1. stirringstirred for 10 min
  2. washThe resulting mixture was washed with citric acid, saturated aqueous sodium bicarbonate, and saturated brine
  3. customevaporated in vacuo
  4. customThe crude product was purified by column chromatography on silica gel (gradient of EtOAc:DCM 0:100 to 30:70)

Sources & evidence

ORD record
ord-1df82f74d2d248578016e252c28a42bd
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

Loading…