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 714689ノート

反応式

HRID 714689 の反応式
[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

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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]

出典と根拠

ORDレコード
ord-e74fc04c959846dabfcf66ff7845165d
出典データセット
uspto-grants-2015_11
特許番号
US09187466B2

反応ノート

読み込み中…