Dichloromethane → HCID 69558215, compound

HRID 1934420Notes

Reaction equation

HRID 1934420 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][CH:24]=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][CH:24]=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 224664924-Chloro-6-ethyl-2-(methylthio)-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 69558215HCID 69558215, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 0.70 g (28.3 mmol) of sodium hydride in 40 mL of benzene was added 1.90 g (24.5 mmol) of methyl glycolate and 6.00 g (18.9 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine. The mixture was heated at 60° C. and monitored by TLC (silica, methylene chloride) for conversion to product. After 3 days, an additional 0.70 g (28.3 mmol) of sodium hydride and 1.90 g (24.5 mmol) of methyl glycolate was added to the reaction. After an additional 3 days, the reaction was cooled to ambient temperature and partitioned by the addition of 100 mL of 2 M sodium hydrogen sulfate and 200 mL of ethyl acetate. The aqueous phase was extracted twice with 50 mL portions of ethyl acetate. The-combined organic phases were dried with magnesium sulfate and concentrated to 7.85 g of yellow solid. The solid was purified by flash chromatography (500 g silica, step gradient from 1:1 heptane-methylene chloride to methylene chloride) to provide 6.35 g (90%) of [[2-(methylthio)-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a white solid. nmr (500 MHz, CDCl3) δ1.25 (t, J=7.5 Hz, 3H), 2.54 (s, 3H), 2.58 (q, J=7.5 Hz, 2H), 3.79 (s, 3H), 5.05 (s, 2H), 5.40 (s, 2H), 6.30 (s, 1H), 7.07 (d, J=7.1 Hz, 2H), 7.24 (m, 3H)

Workup

  1. waitAfter an additional 3 days
  2. temperaturethe reaction was cooled to ambient temperature
  3. custompartitioned by the addition of 100 mL of 2 M sodium hydrogen sulfate and 200 mL of ethyl acetate
  4. extractionThe aqueous phase was extracted twice with 50 mL portions of ethyl acetate
  5. dry with materialThe-combined organic phases were dried with magnesium sulfate
  6. concentrationconcentrated to 7.85 g of yellow solid
  7. customThe solid was purified by flash chromatography (500 g silica, step gradient from 1:1 heptane-methylene chloride to methylene chloride)

Sources & evidence

ORD record
ord-564cb2273ad24f619a12b209d7227247
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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