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 1823984Notes

Reaction equation

HRID 1823984 reaction equation
[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

Participants

7

Reactant 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

Product 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'-dioxideYield 23%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-aea50cc83aca4748ad66475a70fffee5
Source dataset
uspto-grants-2006_05
Patent number
US07041689B2

Reaction notes

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