Ammonium Chloride → HCID 86649068, 화합물

HRID 1801967노트

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HRID 1801967 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][C:19]=1[O:26][CH3:27].CC1CCCO1.[Cl-].[NH4+]>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])=[C:19]([O:26][CH3:27])[CH:20]=2)=[O:14])[N:3]=1

참가 물질

5

반응물 3

HCID 25517Ammonium ChlorideHCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178426731HCID 178426731, 화합물2회

생성물 1

HCID 86649068HCID 86649068, 화합물수율 62.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-35 °C

실험 절차

To a stirred mixture of ethyl 4-chloroquinazoline-2-carboxylate (500 mg, 2.11 mmol) in THF (17 mL) at −40° C. was added dropwise 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (2.53 mL, 2.53 mmol). The reaction mixture was stirred at −30 to −40° C. for 3 h. Additional 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (1.05 mL, 1.05 mmol) was added and stirring was continued at −30 to −40° C. for an additional 1.5 h. To the mixture was added saturated aq ammonium chloride (25 mL) and the mixture was allowed to warm to rt. The mixture was extracted with EtOAc (2×) and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with diethyl ether and the resulting solid was collected by filtration and dried to afford (4-chloroquinazolin-2-yl)(4-fluoro-3-methoxyphenyl)methanone as a colorless solid (417 mg, 62%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.92 (s, 3H), 7.42 (dd, J=11.1, 8.7 Hz, 1H), 7.64 (m, 1H), 7.85 (d, J=8.4 Hz, 1H), 8.04 (m, 1H), 8.23-8.25 (m, 2H), 8.43 (d, J=8.4 Hz, 1H); LC-MS (ESI) m/z 317 (M+H)+.

후처리

  1. stirringstirring
  2. waitwas continued at −30 to −40° C. for an additional 1.5 h
  3. temperatureto warm to rt
  4. extractionThe mixture was extracted with EtOAc (2×)
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with diethyl ether
  9. filtrationthe resulting solid was collected by filtration
  10. customdried

출처 및 근거

ORD 기록
ord-e75689692b6d4c22906c057bea620288
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08349851B2

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