Dichloromethane → HCID 69558084, compound

HRID 1934434Notes

Reaction equation

HRID 1934434 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]=[C:25]([F:29])[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]=[C:25]([F:29])[CH:24]=3)[C:15]=2[N:16]=[C:11]([S:10][CH3:9])[N:12]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 66774Methyl GlycolateHCID 22466488HCID 22466488, compound

Product 1

HCID 69558084HCID 69558084, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
57 °C

Procedure

To a suspension of 82 mg (3.43 mmol) of sodium hydride in 4 mL of benzene was added 315 mg (3.43 mmol) of methyl glycolate and a solution of 384 mg (1.14 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-[(3-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidine in 4 ml of benzene. The mixture was heated at 57° C. and monitored by TLC (silica, methylene chloride) for conversion to product. After 2 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 600 mg of solid. The product was purified by flash chromatography (54 g silica, hexane-ethyl acetate gradient 100:0 to 75:25) to provide 211 mg (48%) of [[2-(methylthio)-6-ethyl-7-[(3-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a white solid. nmr (300 MHz, CDCl3) δ1.14 (t, 3H), 2.53 (s, 3H), 2.55 (q, 2H), 3.88 (s, 3H), 5.04 (s, 2H), 5.36 (s, 2H), 6.30 (s, 1H), 6.75 (d, 1H), 6.85 (d, 1H), 6.96 (dt, 1H), 7.26 (dt, 1H)

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. custompartitioned by the addition of 15 mL of 2 M sodium hydrogen sulfate and 15 mL of ethyl acetate
  3. extractionThe aqueous phase was extracted twice with 7 mL portions of ethyl acetate
  4. dry with materialThe combined organic phases were dried with sodium sulfate
  5. concentrationconcentrated 600 mg of solid
  6. customThe product was purified by flash chromatography (54 g silica, hexane-ethyl acetate gradient 100:0 to 75:25)

Sources & evidence

ORD record
ord-49a47c671075425c8701031a7c65fe30
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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