Dichloromethane → [[2-(methylthio)-6-ethyl-7-([1,1'-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester

HRID 1934438Notes

Reaction equation

HRID 1934438 reaction equation
[H-].[Na+].[C:3]([O:7][CH3:8])(=[O:6])[CH2:4][OH:5].[CH3:9][S:10][C:11]1[N:12]=[C:13](Cl)[C:14]2[CH:19]=[C:18]([CH2:20][CH3:21])[N:17]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:15]=2[N:16]=1.C(Cl)Cl>C1C=CC=CC=1>[CH3:8][O:7][C:3](=[O:6])[CH2:4][O:5][C:13]1[C:14]2[CH:19]=[C:18]([CH2:20][CH3:21])[N:17]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:15]=2[N:16]=[C:11]([S:10][CH3:9])[N:12]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydride2×HCID 66774Methyl Glycolate2×HCID 22466482HCID 22466482, compound

Product 1

HCID 69558384[[2-(methylthio)-6-ethyl-7-([1,1'-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a suspension of 64 mg (2.66 mmol) of sodium hydride in 5 mL of benzene was added 200 mg (2.22 mmol) of methyl glycolate and a solution of 350 mg (0.89 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine in 2.5 ml of benzene then the mixture heated to 60° C. The reaction was monitored for conversion to product by TLC (silica, methylene chloride). Additional sodium hydride (96 mg) and methyl glycolate (360 mg) were added in portions over 4 days. The reaction was cooled to ambient temperature and partitioned by the addition of 15 mL of 2 M sodium hydrogen sulfate and 15 mL of ethyl acetate. The aqueous phase was extracted twice with 7 mL portions of ethyl acetate. The combined organic phases were dried with sodium sulfate and concentrated. The product was purified by flash chromatography (53 g silica, hexanes-ethyl acetate gradient 100:0 to 85:15) to provide 187 mg (47%) of [[2-(methylthio)-6-ethyl-7-([1,1′-biphenyl]-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a solid. nmr (300 MHz, CDCl3) δ1.10 (t, 3H), 2.16 (q, 2H), 2.52 (s, 3H), 3.80 (s, 3H), 5.03 (s, 2H), 5.32 (s, 2H), 6.25 (s, 1H), 6.62 (d, 1H), 7.1-7.6 (m, 8H)

Workup

  1. custompartitioned by the addition of 15 mL of 2 M sodium hydrogen sulfate and 15 mL of ethyl acetate
  2. extractionThe aqueous phase was extracted twice with 7 mL portions of ethyl acetate
  3. dry with materialThe combined organic phases were dried with sodium sulfate
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography (53 g silica, hexanes-ethyl acetate gradient 100:0 to 85:15)

Sources & evidence

ORD record
ord-4b2351ba94d246e8bd29fce27dd04895
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

Loading…