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 1823984노트

반응식

HRID 1823984 반응식
[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

참가 물질

7

반응물 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

생성물 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'-dioxide수율 23%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-aea50cc83aca4748ad66475a70fffee5
출처 데이터셋
uspto-grants-2006_05
특허 번호
US07041689B2

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