Cesium carbonate → Methyl 2-(3((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methylpyridine-6-carboxylate

HRID 1748215Notes

Reaction equation

HRID 1748215 reaction equation
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([O:9][CH2:10][C:11]1[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:29])([F:28])[F:27])=[N:13][O:14][C:15]=1[CH:16]1[CH2:18][CH2:17]1)[CH2:2]2.C[C:31](N(C)C)=[O:32].Cl[C:37]1[CH:46]=[C:45]([CH3:47])[C:40](C(OC)=O)=[CH:39][N:38]=1.[C:48](=O)([O-])[O-:49].[Cs+].[Cs+]>O>[CH:16]1([C:15]2[O:14][N:13]=[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:28])([F:27])[F:29])[C:11]=2[CH2:10][O:9][CH:3]2[CH2:2][CH:1]3[N:8]([C:39]4[CH:40]=[C:45]([CH3:47])[CH:46]=[C:37]([C:48]([O:32][CH3:31])=[O:49])[N:38]=4)[CH:5]([CH2:6][CH2:7]3)[CH2:4]2)[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 46223836Methyl 6-chloro-4-methylpyridine-3-carboxylateHCID 67983256HCID 67983256, compound

Product 1

HCID 118590192Methyl 2-(3((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methylpyridine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

The amine, 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)-isoxazole (125 mg, 0.31 mmol), dimethylacetamide (1.5 mL), methyl 6-chloro-4-methylnicotinate (157 mg, 0.93 mmol), and cesium carbonate (303 mg, 0.93 mmol) were combined sequentially and heated to 60° C. for 2 hours. The mixture was diluted with water and extracted with ethyl acetate (2×10 mL). The organics were dried (MgSO4) then evaporated in vacuo. The product was purified by flash silica chromatography with a gradient of 0-100% ethyl acetate/hexanes to furnish the desired compound as a clear oil.

Workup

  1. extractionextracted with ethyl acetate (2×10 mL)
  2. dry with materialThe organics were dried (MgSO4)
  3. customthen evaporated in vacuo
  4. customThe product was purified by flash silica chromatography with a gradient of 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8d7095dab6c44e2d8fe10166fa061f4a
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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