Cesium fluoride → HCID 117843507, compound

HRID 2209235Notes

Reaction equation

HRID 2209235 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:11][C@@H:12]([C@H:14]2[CH2:18][N:17]([C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH3:20])[C:16](=[O:29])[CH2:15]2)[CH3:13])[C:5]2[N:6]([N:8]=[CH:9][CH:10]=2)[CH:7]=1.[CH3:30][N:31]1[C:35]2[CH:36]=[C:37]([Sn](CCCC)(CCCC)CCCC)[S:38][C:34]=2[CH:33]=[N:32]1.[F-].[Cs+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([C@H:19]([N:17]2[CH2:18][C@H:14]([C@H:12]([O:11][C:4]3[C:5]4[N:6]([N:8]=[CH:9][CH:10]=4)[CH:7]=[C:2]([C:37]4[S:38][C:34]5[CH:33]=[N:32][N:31]([CH3:30])[C:35]=5[CH:36]=4)[CH:3]=3)[CH3:13])[CH2:15][C:16]2=[O:29])[CH3:20])=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 71143890HCID 71143890, compoundHCID 117842669HCID 117842669, compound

Product 1

HCID 117843507HCID 117843507, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (R)-4-((R)-1-((6-bromopyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 6.01 (30 mg, 0.065 mmol) and 1-methyl-5-(tributylstannyl)-1H-thieno[3,2-c]pyrazole (36 mg, 0.085 mmol, prepared according to protocols described in WO2012/177714 and US2012/043276) were dissolved in DMF (0.6 mL). Cesium fluoride (20 mg, 0.13 mmol), cuprous iodide (2.5 mg, 0.013 mmol) and Pd(PPh3)4 (7.6 mg, 0.0066 mmol) were added. Argon gas was bubbled through the reaction mixture for 2 minutes and the reaction was heated to 50° C. for 16 h. The reaction was cooled to room temperature, EtOAc and water were added, the layers were separated and the aqueous layer was extracted with EtOAc (1x). The combined organics were washed with water, dried (MgSO4), filtered and concentrated to a residue which was purified by silica gel chromatography (0-5% MeOH in EtOAc) to afford (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-((R)-1-((6-(1-methyl-1H-thieno[3,2-c]pyrazol-5-yl)pyrazolo[1,5-a]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one 6.28.

Workup

  1. customArgon gas was bubbled through the reaction mixture for 2 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. additionEtOAc and water were added
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (1x)
  6. washThe combined organics were washed with water
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to a residue which
  10. customwas purified by silica gel chromatography (0-5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-a361a7b76fb14fb6a77521b2bafb9199
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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