Chloride → Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate

HRID 1508914노트

반응식

HRID 1508914 반응식
Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[N:3]=1.CC1(C)C(C)(C)OB([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:29][CH:28]=2)O1.C([O-])([O-])=O.[Na+].[Na+].[Cl-]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.O1CCOCC1>[Cl:17][C:13]1[CH:12]=[C:11]([C:4]2[N:3]=[C:2]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[CH:7]=[C:6]([CH:8]3[CH2:10][CH2:9]3)[N:5]=2)[CH:16]=[CH:15][CH:14]=1

참가 물질

8

반응물 4

HCID 312ChlorideHCID 10340Sodium CarbonateHCID 633553904-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyrimidineHCID 674944814-(2-Methoxy-2-oxoethyl)benzylboronic Acid Pinacol Ester

생성물 1

HCID 90112009Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate수율 52.6%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A 20-mL sealed tube, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6-cyclopropylpyrimidine (0.365 g, 1.38 mol), methyl 2-(4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)phenyl)acetate (0.400 g, 1.38 mmol), Pd(dppf)Cl2 (0.113 g, 0.14 mmol), and powdered Na2CO3 (0.438 g, 4.14 mmol). Dioxane (6 mL) and water (3 mL) were added. The resulting mixture was stirred under Ar at 90° C. for 1.5 h until the starting chloride was consumed. After cooling to room temperature, the reaction mixture was filtered through celite washing with ethyl acetate until the filtrate was colorless. The aqueous layer was separated and the organic layer was washed with saturated sodium chloride (2×5 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (95:5 to 1:2) as eluent to afford the title compound (0.285 g, 52%) as a colorless oil. MW=392.88. 1H NMR (DMSO-d6, 500 MHz) δ 8.30-8.27 (m, 2H), 7.59-7.51 (m, 2H), 7.31 (d, J=8.0 Hz, 2H), 7.28 (s, 1H), 7.21 (d, J=8.0 Hz, 2H), 4.07 (s, 2H), 3.64 (s, 2H), 3.59 (s, 3H), 2.16-2.09 (m, 1H), 1.16-1.05 (m, 4H); ESI MS m/z 393 [M+H]+.

후처리

  1. customA 20-mL sealed tube
  2. customwas consumed
  3. filtrationthe reaction mixture was filtered
  4. washthrough celite washing with ethyl acetate until the filtrate
  5. customThe aqueous layer was separated
  6. washthe organic layer was washed with saturated sodium chloride (2×5 mL)
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on silica

출처 및 근거

ORD 기록
ord-d4fb77e3c2d549c0b951caf44bc4dae3
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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