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

HRID 1473402

反応式

HRID 1473402 の反応式
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

参加物

11

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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)+

後処理

  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)

出典と根拠

ORDレコード
ord-d9acc66ef21e415a80b17a51e6ebc392
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

関連ノート

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