Phosphorus oxychloride → 4-Chloro-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidine

HRID 625031Notes

Reaction equation

HRID 625031 reaction equation
[CH3:1][CH:2]1[C:10]2[C:9](O)=[N:8][CH:7]=[N:6][C:5]=2[CH2:4][S:3]1.O=P(Cl)(Cl)[Cl:14]>>[Cl:14][C:9]1[C:10]2[CH:2]([CH3:1])[S:3][CH2:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178435045HCID 178435045, compound

Product 1

HCID 717438984-Chloro-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidineYield 54%

Procedure

5-Methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-ol (10 g, 59.54 mmol) in POCl3 (100 mL) was heated to reflux for 15 minutes. After cooling, excess POCl3 was removed under vacuum. The residue was dissolved in CH2Cl2 (100 mL) and saturated NaHCO3 (400 mL) was added at 0° C. The reaction mixture was stirred for 1 hour. The aqueous phase was extracted with DCM (3×250 mL). The organic phase was combined, dried and concentrated. The residue was purified by silica gel chromatography, eluting with Hexane/ethyl acetate (4:1) to give 4-chloro-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidine (6 g, 54%). 1H NMR (CDCl3, 400 MHz) δ 8.80 (s, 1H), 4.68 (m, 1H), 4.44 (m, 1H), 4.13 (d, J=16.8 Hz, 2H), 1.68 (d, J=7.2 Hz, 3H).

Workup

  1. temperatureto reflux for 15 minutes
  2. temperatureAfter cooling
  3. customexcess POCl3 was removed under vacuum
  4. dissolutionThe residue was dissolved in CH2Cl2 (100 mL)
  5. additionsaturated NaHCO3 (400 mL) was added at 0° C
  6. extractionThe aqueous phase was extracted with DCM (3×250 mL)
  7. customdried
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with Hexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-c6bffdf48d9247f8968804a9de2f8867
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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