Cesium carbonate → HCID 178472377、化合物

HRID 928146ノート

反応式

HRID 928146 の反応式
Br[C:2]1[S:6][C:5]([C:7]([C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]2)([OH:10])[CH2:8][F:9])=[N:4][CH:3]=1.[CH3:22][C:23]1[CH:24]=[C:25]([NH:38][C:39]2[N:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][N:40]=2)[CH:26]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:28]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O.O1CCOCC1>[F:9][CH2:8][C:7]([C@H:11]1[CH2:16][CH2:15][C@H:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1)([OH:10])[C:5]1[S:6][C:2]([C:27]2[CH:26]=[C:25]([NH:38][C:39]3[N:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][N:40]=3)[CH:24]=[C:23]([CH3:22])[CH:28]=2)=[CH:3][N:4]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 178472376HCID 178472376、化合物

生成物 1

HCID 178472377HCID 178472377、化合物

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Racemic ethyl trans-4-[1-(5-bromo-1,3-thiazol-2-yl)-2-fluoro-1-hydroxyethyl]cyclohexane-carboxylate (107 mg, 0.281 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (231 mg, 0.610 mmol), X-Phos (56 mg, 0.120 mmol), Pd2(dba)3 (52 mg, 0.056 mmol), cesium carbonate (429 mg, 1.32 mmol), 1,4-dioxane (3.0 ml) and water (0.3 ml) were combined and the vial was evacuated and purged with nitrogen 3 times then heated to 100° C. for 2 h. The mixture was then filtered and diluted with EtOAc. The organic phase was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified on silica gel (0-10% MeOH in DCM) to afford racemic ethyl trans-4-{2-fluoro-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate which was used without further purification. MS ESI calc'd. for C26H28F4N4O3S [M+H]+ 553. found 553.

後処理

  1. customthe vial was evacuated
  2. custompurged with nitrogen 3 times
  3. filtrationThe mixture was then filtered
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on silica gel (0-10% MeOH in DCM)

出典と根拠

ORDレコード
ord-da5e36387072404d93045ba7d22b9ca0
出典データセット
uspto-grants-2016_03
特許番号
US09290490B2

反応ノート

読み込み中…