Cesium carbonate → Methyl 1-(1-cyclopropyl-6-{[6-(1-methyl-1H-pyrazol-4-yl)-4-oxospiro[chroman-2,4'-piperidin]-1'-yl]carbonyl}-1H-indol-4-yl)piperidine-4-carboxylate

HRID 38466Notes

Reaction equation

HRID 38466 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].FC(F)(F)S(O[C:13]1[CH:21]=[C:20]([C:22]([N:24]2[CH2:29][CH2:28][C:27]3([CH2:38][C:37](=[O:39])[C:36]4[C:31](=[CH:32][CH:33]=[C:34]([C:40]5[CH:41]=[N:42][N:43]([CH3:45])[CH:44]=5)[CH:35]=4)[O:30]3)[CH2:26][CH2:25]2)=[O:23])[CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH:46]1[CH2:48][CH2:47]1)(=O)=O.[NH:51]1[CH2:56][CH2:55][CH:54]([C:57]([O:59][CH2:60]C)=[O:58])[CH2:53][CH2:52]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:46]1([N:17]2[C:18]3[C:14](=[C:13]([N:51]4[CH2:56][CH2:55][CH:54]([C:57]([O:59][CH3:60])=[O:58])[CH2:53][CH2:52]4)[CH:21]=[C:20]([C:22]([N:24]4[CH2:25][CH2:26][C:27]5([CH2:38][C:37](=[O:39])[C:36]6[C:31](=[CH:32][CH:33]=[C:34]([C:40]7[CH:41]=[N:42][N:43]([CH3:45])[CH:44]=7)[CH:35]=6)[O:30]5)[CH2:28][CH2:29]4)=[O:23])[CH:19]=3)[CH:15]=[CH:16]2)[CH2:47][CH2:48]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 70770Ethyl 4-piperidinecarboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 582087121-cyclopropyl-6-{[6-(1-methyl-1H-pyrazol-4-yl)-4-oxospiro[chroman-2,4'-piperidin]-1'-yl]carbonyl}-1H-indol-4-yl trifluoromethanesulfonate

Product 1

HCID 67055541Methyl 1-(1-cyclopropyl-6-{[6-(1-methyl-1H-pyrazol-4-yl)-4-oxospiro[chroman-2,4'-piperidin]-1'-yl]carbonyl}-1H-indol-4-yl)piperidine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Cs2CO3 (261 mg, 0.800 mmol), Pd(OAc)2 (8.98 mg, 0.040 mmol), 1-cyclopropyl-6-{[6-(1-methyl-1H-pyrazol-4-yl)-4-oxospiro[chroman-2,4′-piperidin]-1′-yl]carbonyl}-1H-indol-4-yl trifluoromethanesulfonate (251 mg, 0.4 mmol), ethyl 4-piperidinecarboxylate (94.0 mg, 0.600 mmol) and biphenyl-2-yl(di-tert-butyl)phosphine (11.9 mg, 0.0400 mmol) were suspended in 1,4-dioxane (3 ml) and the mixture was stirred at 100° C. overnight. The mixture was filtered through celite pad, washing with CHCl3, and the solvent was evaporated under reduced pressure. The residue was purified by silicagel column chromatography (CHCl3/MeOH), then preparative-TLC (CHCl3/MeOH) to give intended compound as brown oil.

Workup

  1. filtrationThe mixture was filtered through celite pad
  2. washwashing with CHCl3
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by silicagel column chromatography (CHCl3/MeOH)
  5. custompreparative-TLC (CHCl3/MeOH) to give

Sources & evidence

ORD record
ord-2e513f059c534c47bb77afa38ccd88a4
Source dataset
uspto-grants-2013_09
Patent number
US08524730B2

Reaction notes

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