Potassium Phosphate, Tribasic → 5-(4-Chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2-({2-[2-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 714689노트

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HRID 714689 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:21][C@H:22]([OH:27])[C:23]([F:26])([F:25])[F:24])[C:10](=[O:20])[N:11]([CH2:13][C:14]3[S:18][C:17](Cl)=[N:16][CH:15]=3)[N:12]=2)=[CH:4][CH:3]=1.[F:28][C:29]([F:40])([F:39])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.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]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([CH2:21][C@H:22]([OH:27])[C:23]([F:26])([F:24])[F:25])[C:10](=[O:20])[N:11]([CH2:13][C:14]3[S:18][C:17]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[C:29]([F:40])([F:39])[F:28])=[N:16][CH:15]=3)[N:12]=2)=[CH:6][CH:7]=1

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 674078775-(4-Chlorophenyl)-2-[(2-chloro-1,3-thiazol-5-yl)methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

생성물 1

HCID 866909205-(4-Chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2-({2-[2-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
110 °C

실험 절차

Under an atmosphere of argon, 62 mg (0.14 mmol) of the compound from Example 31A and 40 mg (0.21 mmol) of 2-(trifluoromethyl)phenylboronic acid were dissolved in 2 ml of toluene. 6.5 mg (0.007 mmol) of tris(dibenzylideneacetone)dipalladium, 5.6 mg (0.014 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl and 60 mg (0.28 mmol) of potassium phosphate were then added, and under argon the mixture was heated to 110° C. for 48 h. For work-up, the mixture was diluted at RT with 10 ml of ethyl acetate and 10 ml of water, the organic phase was separated off and the aqueous phase was extracted two more times with in each case 10 ml of ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified chromatographically [Method 19]. This gave 10 mg (13% of theory) of the target compound.

후처리

  1. customthe organic phase was separated off
  2. extractionthe aqueous phase was extracted two more times with in each case 10 ml of ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified chromatographically [Method 19]

출처 및 근거

ORD 기록
ord-e74fc04c959846dabfcf66ff7845165d
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187466B2

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