Benzyl mercaptan → 6-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine

HRID 1473402

반응식

HRID 1473402 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](Cl)=[N:7][N:6]=[CH:5]2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.[CH3:72][O:73][C:74]1[CH:79]=[C:78]([C:80]([F:83])([F:82])[F:81])[CH:77]=[CH:76][C:75]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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].C(Cl)Cl.O>[CH2:64]([S:71][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:75]1[CH:76]=[CH:77][C:78]([C:80]([F:83])([F:82])[F:81])=[CH:79][C:74]=1[O:73][CH3:72])=[N:7][N:6]=[CH:5]2)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

참가 물질

11

반응물 6

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 220304246-Bromo-1-chlorophthalazineHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acid

생성물 1

HCID 866874486-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine수율 43.1%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

A solution of 6-bromo-1-chlorophthalazine (0.500 g, 2.053 mmol), Pd2(dba)3 (0.047 g, 0.051 mmol), Xantphos (0.059 g, 0.103 mmol), and n,n-diisopropylethylamine (1.076 ml, 6.16 mmol) in 6 mL of dioxane was heated to 60° C. and was treated with benzyl mercaptan (0.243 ml, 2.053 mmol) drop wise. After stirring for one hour, LC/MS showed product and bis coupled product. (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.407 g, 1.848 mmol), potassium carbonate (1.135 g, 8.21 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.168 g, 0.205 mmol), and 2 mL of water were added and the reaction mixture was heated to 80° C. overnight. LC/MS showed mostly product, so the reaction mixture was allowed to cool to room temperature. The aqueous layer was removed, and the organics were concentrated. Purification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 6-(benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine (0.340 g, 0.797 mmol, 38.8% yield). m/z (ESI) 427.2 (M+H)+

후처리

  1. temperatureto cool to room temperature
  2. customThe aqueous layer was removed
  3. concentrationthe organics were concentrated
  4. customPurification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-d9acc66ef21e415a80b17a51e6ebc392
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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