Thiophenol → [[2-(phenylthio)-5-(aminooxoacetyl)-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester

HRID 1934428Notes

Reaction equation

HRID 1934428 reaction equation
[H-].[Na+].[C:3]1([SH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12](=[O:42])[CH2:13][O:14][C:15]1[C:16]2[C:27]([C:28](=[O:32])[C:29]([NH2:31])=[O:30])=[C:26]([CH2:33][CH3:34])[N:25]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:17]=2[N:18]=[C:19](S(C)(=O)=O)[N:20]=1>O1CCCC1>[CH3:10][O:11][C:12](=[O:42])[CH2:13][O:14][C:15]1[C:16]2[C:27]([C:28](=[O:32])[C:29]([NH2:31])=[O:30])=[C:26]([CH2:33][CH3:34])[N:25]([CH2:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:17]=2[N:18]=[C:19]([S:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:20]=1

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 24758Sodium hydrideHCID 69558105[[2-(methylsulfonyl)-5-(aminooxoacetyl)-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy] acetic acid methyl ester

Product 1

HCID 69558065[[2-(phenylthio)-5-(aminooxoacetyl)-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl esterYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a slurry of 5.4 mg (0.23 mmol) of sodium hydride in 1.0 mL of tetrahydrofuran was added 0.025 mL of thiophenol followed by 100 mg (0.21 mmol) of [[2-(methylsulfonyl)-5-(aminooxoacetyl)-6-ethyl-7-(phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester and the mixture heated to 55° C. for 18 hours. The reaction was cooled to ambient temperature and partitioned between 10 mL of methylene chloride and 10 mL of 0.2 M sodium hydrogen sulfate. The organic portion was dried with magnesium sulfate and concentrated to a solid. The crude material was purified by flash chromatography (5.0 g silica, ethyl acetate) to provide 52 mg (49%) of [[2-(phenylthio)-5-(aminooxoacetyl)-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) δ1.14 (t, J=7.4 Hz, 3H), 2.94 (q, J=7.4 Hz, 2H), 3.72 (s, 3H), 4.81 (s, 2H), 5.34 (s, 2H), 5.59 (s, 1H), 6.54 (s, 1H), 7.10 (m, 2H), 7.28 (m, 3H), 7.40 (m, 3H), 7.62 (m, 2H)

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. custompartitioned between 10 mL of methylene chloride and 10 mL of 0.2 M sodium hydrogen sulfate
  3. dry with materialThe organic portion was dried with magnesium sulfate
  4. concentrationconcentrated to a solid
  5. customThe crude material was purified by flash chromatography (5.0 g silica, ethyl acetate)

Sources & evidence

ORD record
ord-6ff66e6df1a14da6ac5cd52de5b8fa14
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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