Morpholine → HCID 66855589, compound

HRID 2282229Notes

Reaction equation

HRID 2282229 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[C:14]([CH3:38])[C:15]([C:16]3[S:17][C:18]([C:27]4[N:31]=[CH:30][N:29]([CH:32]5[CH2:37][CH2:36][CH2:35][CH2:34][O:33]5)[N:28]=4)=[C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[N:20]=3)=[C:9]2[CH:8]=1)(=O)=O.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:38][C:14]1[C:15]([C:16]2[S:17][C:18]([C:27]3[N:31]=[CH:30][N:29]([CH:32]4[CH2:37][CH2:36][CH2:35][CH2:34][O:33]4)[N:28]=3)=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:20]=2)=[C:9]2[CH:8]=[C:7]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[CH:12]=[CH:11][N:10]2[N:13]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86649599HCID 86649599, compound

Product 1

HCID 66855589HCID 66855589, compoundYield 56.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A suspension 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-yl trifluoromethanesulfonate (150 mg, 0.25 mmol) obtained in Example 82-B(i), morpholine (501 mg, 5.73 mmol), tris(dibenzylideneacetone)dipalladium (0) (45 mg, 0.049 mmol), (R)-BINAP (50 mg, 0.080 mmol) and cesium carbonate (720 mg, 2.21 mmol) in toluene (30 mL) was stirred at 110° C. for 1 h. The reaction mixture was allowed to cool to room temperature, and then water (150 mL) was added. The mixture was extracted with EtOAc (150 mL×2). The combined organic layers were dried over anhydrous magnesium sulfate and insoluble materials were removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography (EtOAc/hexane=10/90→100/0) to give the title compound (75 mg, 56%) as a yellow solid.

Workup

  1. extractionThe mixture was extracted with EtOAc (150 mL×2)
  2. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate and insoluble materials
  3. customwere removed by filtration
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by silica gel column chromatography (EtOAc/hexane=10/90→100/0)

Sources & evidence

ORD record
ord-fb9f4e82c3434ce0904dea2d3159542b
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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