5-bromo-2-chloro-3-methylpyrimidin-4(3H)-one → 5-bromo-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one

HRID 2241306노트

반응식

HRID 2241306 반응식
[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[C:5](Cl)=[N:6][CH:7]=1.[Br-].[CH:12]1([CH2:18][Zn+])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[C:5]([CH2:18][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[N:6][CH:7]=1

참가 물질

5

반응물 2

HCID 673486115-bromo-2-chloro-3-methylpyrimidin-4(3H)-oneHCID 178419774HCID 178419774, 화합물

생성물 1

HCID 685170185-bromo-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one수율 37%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
100 °C

실험 절차

A solution of 5-bromo-2-chloro-3-methylpyrimidin-4(3H)-one (0.100 g, 0.448 mmol; prepared according to the procedure of Example 46, Step B) and PdCl2(PPh3)2 (0.016 g, 0.022 mmol) in THF (2.5 mL) was sparged with N2, and then (cyclohexylmethyl)zinc(II)bromide (0.904 ml, 0.452 mmol; 0.5 M solution in THF) was added. The reaction mixture was stirred at 100° C. for 1.5 hours. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude material was purified by flash column chromatography, eluting with 10:1 CH2Cl2/EtOAc to afford 0.047 g (37%) of the product as a waxy yellow solid. LRMS (APCI pos) m/e 285, 287 (M+, Br pattern).

후처리

  1. customprepared
  2. customwas sparged with N2
  3. temperatureThe reaction mixture was cooled to room temperature
  4. custompartitioned between EtOAc and H2O
  5. extractionThe aqueous layer was re-extracted with EtOAc (1×)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by flash column chromatography
  10. washeluting with 10:1 CH2Cl2/EtOAc

출처 및 근거

ORD 기록
ord-5d5d19c72f8d4f228e95fe0e925768ef
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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