Phosphorus oxychloride → HCID 86647812, compound

HRID 240999Notes

Reaction equation

HRID 240999 reaction equation
[CH3:1][CH:2]1[CH2:13][C:5]2[N:6]=[C:7]([S:11][CH3:12])[NH:8][C:9](=O)[C:4]=2[CH2:3]1.P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:9]1[C:4]2[CH2:3][CH:2]([CH3:1])[CH2:13][C:5]=2[N:6]=[C:7]([S:11][CH3:12])[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1363315341256955-59-5

Product 1

HCID 86647812HCID 86647812, compoundYield 12%

Procedure

A solution of 6-methyl-2-(methylthio)-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one (0.19 g, 0.97 mmol) in phosphorous oxychloride (5.0 mL) was heated to 95° C. for 1 hour. After cooling the reaction was concentrated, and the residue dissolved in ethyl acetate (50 mL) and washed with cold water (25 mL), 0.1 M aqueous sodium hydroxide (25 mL) and brine (20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (diethyl ether/hexanes, 1:10) and the product containing fractions concentrated. The residue thus obtained was purified further by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile to give 4-chloro-6-methyl-2-(methylthio)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (25 mg, 12% yield) as an oil. 1H NMR (400 MHz, d6-DMSO): 3.12 (m, 2H), 2.61 (m, 2H), 2.56 (s, 3H), 1.25 (m, 1H), 1.18 (d, 3H); MS (EI) for C9H11ClN2S: 215 (MH+).

Workup

  1. temperatureAfter cooling the reaction
  2. concentrationwas concentrated
  3. dissolutionthe residue dissolved in ethyl acetate (50 mL)
  4. washwashed with cold water (25 mL), 0.1 M aqueous sodium hydroxide (25 mL) and brine (20 mL)
  5. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel (diethyl ether/hexanes, 1:10)
  9. additionthe product containing fractions
  10. concentrationconcentrated
  11. customThe residue thus obtained
  12. customwas purified further by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile

Sources & evidence

ORD record
ord-0690370fe2f443a6b1cadfdeaf96e7db
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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