Ethyl 4-chloroquinazoline-2-carboxylate → HCID 86649067, compound

HRID 625813Notes

Reaction equation

HRID 625813 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14]CC)=O)[N:3]=1.[Cl:17][C:18]1[CH:19]=[C:20]([Mg]Br)[CH:21]=[CH:22][C:23]=1[F:24].C1COCC1>C1COCC1>[Cl:17][C:18]1[CH:19]=[C:20]([C:12]([C:4]2[N:3]=[C:2]([Cl:1])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:14])[CH:21]=[CH:22][C:23]=1[F:24]

Participants

4

Reactant 2

HCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178420691HCID 178420691, compound2×

Product 1

HCID 86649067HCID 86649067, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A mixture of ethyl 4-chloroquinazoline-2-carboxylate (1 g, 4.2 mmol) in THF (50 mL) was filtered, and to the filtrate at −30° C. under Ar was added 0.5 M (3-chloro-4-fluorophenyl)magnesium bromide/THF (10.4 mL, 5.2 mmol). After stirring at −30° C. for 0.75 h, additional 0.5 M (3-chloro-4-fluorophenyl)magnesium bromide/THF (4.2 mL). After 1 h, the reaction was quenched by addition of saturated aq ammonium chloride and allowed to warm to rt. The mixture was extracted with EtOAc, and the extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford (3-chloro-4-fluorophenyl)(4-chloroquinazolin-2-yl)methanone (495 mg, 37%) which was used directly in the next step. LC-MS (ESI) m/z 321 (M+H)+.

Workup

  1. filtrationwas filtered
  2. waitAfter 1 h
  3. customthe reaction was quenched by addition of saturated aq ammonium chloride
  4. temperatureto warm to rt
  5. extractionThe mixture was extracted with EtOAc
  6. dry with materialthe extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ae067d957c7a4cf48f77d95f8d35362c
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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