Cesium carbonate → [6S,9R,11R]2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(5-methylprid-2-yl)-1-methyl-pyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide

HRID 1823984ノート

反応式

HRID 1823984 の反応式
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][N:8]=2)=[CH:5][C:4](Br)=[N:3]1.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[CH:25][C:26]3[CH2:33][C@H:32]4[C@:34]5([CH2:38][N:37]([CH2:39][C:40]([F:43])([F:42])[F:41])[S:36](=[O:45])(=[O:44])[NH:35]5)[C@H:29]([CH2:30][CH2:31]4)[CH2:28][C:27]=3[CH:46]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:13][C:10]1[CH:11]=[CH:12][C:7]([C:6]2[N:2]([CH3:1])[N:3]=[C:4]([C:23]3[CH:24]=[CH:25][C:26]4[CH2:33][C@H:32]5[C@:34]6([CH2:38][N:37]([CH2:39][C:40]([F:43])([F:42])[F:41])[S:36](=[O:44])(=[O:45])[NH:35]6)[C@H:29]([CH2:30][CH2:31]5)[CH2:28][C:27]=4[CH:46]=3)[CH:5]=2)=[N:8][CH:9]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 221479931-Methyl-3-bromo-5-(5-methylpyridin-2-yl)pyrazoleHCID 23571079[6s,9r,11r]2',3',4',5,5',6,7,8,9,10-Decahydro-2-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide

生成物 1

HCID 23571106[6S,9R,11R]2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(5-methylprid-2-yl)-1-methyl-pyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide収率 23%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A mixture of 1-methyl-3-bromo-5-(5-methylpyridin-2-yl)pyrazole from Step 3 (0.081 g, 0.321 mmol), the homochiral boronate from Example 24 Step 1 (0.156 g, 0.321 mmol), cesium carbonate (0.10 g, 0.32 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.04 g, 10 mol %) in N,N-dimethylformamide (3 mL) and water (1 mL) was degassed and flushed with nitrogen, then stirred at 100° C. under nitrogen for 18 hours. The cooled mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL). The extract was dried (Na2SO4), filtered through a plug of silica gel and concentrated. The residual oil was partitioned between water (10 mL) and diethyl ether (10 mL). The organic layer was dried (Na2SO4) and concentrated. The material was purified by normal-phase preparative HPLC, eluting with ethyl acetate-isohexanes, to give the title compound (0.039 g, 23%) as a beige solid.

後処理

  1. customflushed with nitrogen
  2. additionThe cooled mixture was diluted with water (20 mL)
  3. extractionextracted with ethyl acetate (20 mL)
  4. dry with materialThe extract was dried (Na2SO4)
  5. filtrationfiltered through a plug of silica gel
  6. concentrationconcentrated
  7. customThe residual oil was partitioned between water (10 mL) and diethyl ether (10 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated
  10. customThe material was purified by normal-phase preparative HPLC
  11. washeluting with ethyl acetate-isohexanes

出典と根拠

ORDレコード
ord-aea50cc83aca4748ad66475a70fffee5
出典データセット
uspto-grants-2006_05
特許番号
US07041689B2

反応ノート

読み込み中…