Sodium hydride → HCID 69558414, compound

HRID 1934448Notes

Reaction equation

HRID 1934448 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]([Cl:29])[CH:24]=3)[C:15]=2[N:16]=1>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]([Cl:29])[CH:24]=3)[C:15]=2[N:16]=[C:11]([S:10][CH3:9])[N:12]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 66774Methyl Glycolate2×HCID 22466495HCID 22466495, compound

Product 1

HCID 69558414HCID 69558414, compoundYield 54.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of 79 mg (3.30 mmol) of sodium hydride in 2 mL of benzene was added 225 mg (2.75 mmol) of methyl glycolate and a solution of 320 mg (0.91 mmol) of 2-(methylthio)-4-chloro-6-ethyl-7-[(3-chlorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidine in 2 ml of benzene. The mixture was then heated at 60° C. After 24 hours the reaction was cooled to ambient temperature and an additional 40 mg of sodium hydride and 110 mg of methyl glycolate were added. After 3 days, the reaction was partitioned by the addition of 2 mL of 2 M sodium hydrogen sulfate and 20 mL of ethyl acetate. The organic phase was washed with 10 mL of water, dried with sodium sulfate and concentrated. The product was purified by flash chromatography (30 g silica, methylene chloride-heptane gradient 2:1 to 100:0) to provide 200 mg (54%) of [[2-(methylthio)-6-ethyl-7-[(3-chlorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a white solid. nmr (500 MHz, CDCl3) δ1.26 (t, J=7.4 Hz, 3H), 2.53 (s, 3H), 2.56 (q, J=7.4 Hz, 2H), 3.79 (s, 3H), 5.05 (s, 2H), 5.35 (s, 2H), 6.31 (s, 1H), 6.92 (d, J=6.7 Hz, 1H), 7.08 (s, 1H), 7.21 (m, 2H)

Workup

  1. temperatureAfter 24 hours the reaction was cooled to ambient temperature
  2. customthe reaction was partitioned by the addition of 2 mL of 2 M sodium hydrogen sulfate and 20 mL of ethyl acetate
  3. washThe organic phase was washed with 10 mL of water
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography (30 g silica, methylene chloride-heptane gradient 2:1 to 100:0)

Sources & evidence

ORD record
ord-5f0c986f3471437e8773ab88838871e5
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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