Methyl chloroformate → Methyl 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylate

HRID 928605Notes

Reaction equation

HRID 928605 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[N:15]=[C:16]([Cl:29])[C:17]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:21][S:20][C:18]=2[N:19]=1.Cl[C:31]([O:33][CH3:34])=[O:32]>O1CCCC1.O>[Cl:13][C:14]1[N:15]=[C:16]([Cl:29])[C:17]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:21]([C:31]([O:33][CH3:34])=[O:32])[S:20][C:18]=2[N:19]=1

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 7912DiisopropylamineHCID 127242282,4-Dichloro-5-phenylthieno(2,3-d)pyrimidineHCID 178418339Butyllithium

Product 1

HCID 89579730Methyl 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine-6-carboxylateYield 102.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-55 °C

Procedure

A solution of diisopropylamine (0.755 mL, 5.33 mmol) in dry tetrahydrofuran (10 mL) was cooled with an acetone/cardice bath to −55° C. under a nitrogen atmosphere. Butyllithium in hexanes (2.0 mL, 4.98 mmol, 2.5 M) was added and the temperature was allowed to rise to 0° C. for 10 min. The mixture was cooled to −55° C. and a solution of 2,4-dichloro-5-phenyl-thieno[2,3-d]pyrimidine (1.00 g, 3.56 mmol) in dry tetrahydrofuran (10 mL) was added. The mixture was stirred for 1 hr, maintaining the temperature at −55° C. Methyl chloroformate (0.561 mL, 7.11 mmol) was added and the mixture was allowed to rise to room temperature. It was stirred for 4 hr. Water (20 mL) was added to quench the reaction. The layers were separated and the aqueous was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried (magnesium sulfate), filtered and evaporated to give a brown solid. (1.63 g). This was purified by silica chromatography (50 g cartridge; eluent petroleum ether 40-60/ethyl acetate 0 to 10%; collection by UV trigger). Fractions corresponding to the main peak were combined and evaporated to give the target compound as a yellow solid (1.24 g). m/z [M+H]+338.9/340.9. Retention time 4.89 min (LCMS method+ve 6 min).

Workup

  1. temperaturemaintaining the temperature at −55° C
  2. customto rise to room temperature
  3. stirringIt was stirred for 4 hr
  4. customto quench
  5. customthe reaction
  6. customThe layers were separated
  7. extractionthe aqueous was extracted with ethyl acetate (2×20 mL)
  8. dry with materialThe combined organic layers were dried (magnesium sulfate)
  9. filtrationfiltered
  10. customevaporated
  11. customto give a brown solid
  12. customThis was purified by silica chromatography (50 g cartridge; eluent petroleum ether 40-60/ethyl acetate 0 to 10%; collection by UV trigger)
  13. customevaporated

Sources & evidence

ORD record
ord-cad5b6401cd541f0b52b6703b5ff257b
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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