Cesium carbonate → tert-butyl (1'-benzyl-1-(5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methylcarbamate

HRID 529153Notes

Reaction equation

HRID 529153 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH2:43]([N:50]1[CH2:55][CH2:54][C:53]2([C:63]3[C:58](=[CH:59][CH:60]=[CH:61][C:62]=3[CH2:64][NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[NH:57][CH2:56]2)[CH2:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.Cl[C:74]1[C:75]2[CH:82]([CH:83]([CH3:85])[CH3:84])[CH2:81][CH2:80][C:76]=2[N:77]=[CH:78][N:79]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1(C)C=CC=CC=1>[CH2:43]([N:50]1[CH2:55][CH2:54][C:53]2([C:63]3[C:58](=[CH:59][CH:60]=[CH:61][C:62]=3[CH2:64][NH:65][C:66](=[O:72])[O:67][C:68]([CH3:69])([CH3:71])[CH3:70])[N:57]([C:74]3[C:75]4[CH:82]([CH:83]([CH3:85])[CH3:84])[CH2:81][CH2:80][C:76]=4[N:77]=[CH:78][N:79]=3)[CH2:56]2)[CH2:52][CH2:51]1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86651806Tert-butyl (1'-benzylspiro[indoline-3,4'-piperidine]-4-yl)methylcarbamateHCID 866518154-chloro-5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 86651816tert-butyl (1'-benzyl-1-(5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methylcarbamateYield 69.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with Pd2 dba3 (0.233 g, 0.254 mmol) and Xantphos (0.221 g, 0.381 mmol) and purged with nitrogen. The flask was then charged with tert-butyl (1′-benzylspiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (1.04 g, 2.54 mmol), 4-chloro-5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (0.500 g, 2.54 mmol), Cs2CO3 (1.24 g, 3.81 mmol) and toluene (12.7 mL). The reaction was purged with nitrogen and heated to 100° C. overnight. The reaction was cooled to room temperature and filtered through celite, then GFF, and concentrated under reduced pressure. The crude residue was purified by column chromatography (1-5% MeOH/DCM) to yield tert-butyl (1′-benzyl-1-(5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (1.0 g, 69%). LCMS (APCI+) m/z 568.3 [M+H]+; Rt=4.30 min.

Workup

  1. custompurged with nitrogen
  2. customThe reaction was purged with nitrogen
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered through celite
  5. concentrationGFF, and concentrated under reduced pressure
  6. customThe crude residue was purified by column chromatography (1-5% MeOH/DCM)

Sources & evidence

ORD record
ord-ff768b6fe67b488ba9fd0048379afd23
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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