Ethyl 4-chloroquinazoline-2-carboxylate → (4-Chloroquinazolin-2-yl)(4-fluorophenyl)methanone

HRID 929334노트

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HRID 929334 반응식
[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.[F:17][C:18]1[CH:23]=[CH:22][C:21]([Mg]Br)=[CH:20][CH:19]=1>C1COCC1>[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]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[O:14])[N:3]=1

참가 물질

4

반응물 2

HCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178418676HCID 178418676, 화합물

생성물 1

HCID 86649048(4-Chloroquinazolin-2-yl)(4-fluorophenyl)methanone수율 60%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-40 °C

실험 절차

To a solution of ethyl 4-chloroquinazoline-2-carboxylate 11 (0.6 g, 2.53 mmol) in THF (6 mL) at −40° C. was added dropwise a solution of 4-fluorophenylmagnesium bromide in THF (1 M, 3 mL, 3.0 mmol, 1.2 eq). The reaction mixture was stirred at −40° C. for 4 hrs. The reaction was quenched by addition of 0.5 N HCl (5 mL) and the mixture was extracted with EtOAc (2×10 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The crude product was purified by silica gel chromatography eluting with EtOAc/hexanes to afford compound 12 as a light yellow solid (440 mg, 60%). 1H NMR (300 MHz, DMSO-d6) δ 7.45-7.40 (m, 2H), 8.07-8.03 (m, 1H), 8.17-8.13 (m, 2H), 8.23 (m, 2H), 8.42 (d, 1H); LC-MS (ESI) m/z: 287 (M+H)+.

후처리

  1. customThe reaction was quenched by addition of 0.5 N HCl (5 mL)
  2. extractionthe mixture was extracted with EtOAc (2×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography
  7. washeluting with EtOAc/hexanes

출처 및 근거

ORD 기록
ord-311709244fac4ec4b97534551b3cce0a
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09295672B2

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