Potassium Fluoride → HCID 117842923, compound

HRID 2209077Notes

Reaction equation

HRID 2209077 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C@H:11]2[CH2:15][N:14]([C@@H:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[CH3:17])[C:13](=[O:26])[CH2:12]2)[CH3:10])[C:5]2[N:27]([CH3:30])[CH:28]=[N:29][C:4]=2[CH:3]=1.[O:31]1[CH2:34][CH:33]([N:35]2[CH2:40][CH2:39][N:38]([C:41]3[CH:42]=[N:43][C:44]([Sn](CCCC)(CCCC)CCCC)=[CH:45][CH:46]=3)[CH2:37][CH2:36]2)[CH2:32]1.[F-].[K+]>O1CCOCC1.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>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([C@H:16]([N:14]2[CH2:15][C@H:11]([C@H:9]([O:8][C:6]3[C:5]4[N:27]([CH3:30])[CH:28]=[N:29][C:4]=4[CH:3]=[C:2]([C:44]4[CH:45]=[CH:46][C:41]([N:38]5[CH2:37][CH2:36][N:35]([CH:33]6[CH2:32][O:31][CH2:34]6)[CH2:40][CH2:39]5)=[CH:42][N:43]=4)[N:7]=3)[CH3:10])[CH2:12][C:13]2=[O:26])[CH3:17])=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 117843074(R)-4-((R)-1-(6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneHCID 131735974HCID 131735974, compound

Product 1

HCID 117842923HCID 117842923, compoundYield 100.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Into the mixture of (R)-4-((R)-1-((6-chloro-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.05 (60 mg, 0.14 mmol) and 1-(oxetan-3-yl)-4-(6-(tributylstannyl)pyridin-3-yl)piperazine 7.16 (78 mg, 0.154 mmol) in dioxane (3 mL) was added tetrakis(triphenylphosphine)palladium (16 mg) and KF (24 mg). Then the mixture was flushed with Argon, and heated by microwave at 140° C. for 20 min. The reaction was diluted with 50 mL of ethyl acetate and filtered to remove the solid. After removal of solvent, the residue was purified by silica gel column chromatography to provide 86 mg of (R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-((R)-1-((3-methyl-6-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one. LCMS [M+H]+: 612.27.

Workup

  1. customThen the mixture was flushed with Argon
  2. additionThe reaction was diluted with 50 mL of ethyl acetate
  3. filtrationfiltered
  4. customto remove the solid
  5. customAfter removal of solvent
  6. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1524a7ec05db4d9d9e86ad0ba472b0a9
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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