Cesium carbonate → (R)-tert-butyl 5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 2189997Notes

Reaction equation

HRID 2189997 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:44]1[C:45]2[C@H:52]([CH3:53])[CH2:51][CH2:50][C:46]=2[N:47]=[CH:48][N:49]=1.[Cl:54][C:55]1[CH:56]=[C:57]2[C:63]3([CH2:68][CH2:67][N:66]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[CH2:65][CH2:64]3)[CH2:62][NH:61][C:58]2=[CH:59][CH:60]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[Cl:54][C:55]1[CH:56]=[C:57]2[C:63]3([CH2:64][CH2:65][N:66]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[CH2:67][CH2:68]3)[CH2:62][N:61]([C:44]3[C:45]4[C@H:52]([CH3:53])[CH2:51][CH2:50][C:46]=4[N:47]=[CH:48][N:49]=3)[C:58]2=[CH:59][CH:60]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 46835581Tert-butyl 5-chlorospiro[indoline-3,4'-piperidine]-1'-carboxylateHCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Product 1

HCID 68761290(R)-tert-butyl 5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylateYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A pear-shaped flask was charged with Pd(OAc)2 (2.1 mg, 0.0093 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (8.1 mg, 0.014 mmol) and purged with nitrogen. To the flask was added (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (19 mg, 0.11 mmol), tert-butyl 5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylate (30 mg, 0.093 mmol), Cs2CO3 (45 mg, 0.14 mmol) and toluene (0.9 mL). The mixture was heated at about 100° C. for 4 hours. After cooling to about room temperature, the reaction was diluted with EtOAc, filtered through CELITE® (Celite Corp., Santa Barbara, Calif.), and concentrated. The crude product was purified by column chromatography (hexanes:EtOAc, 5:1 to 3:1) to give (R)-tert-butyl 5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate as an oil (30 mg, 71%). LCMS (APCI+) m/z 455, 457 [M+H]+; Rt=4.14 min.

Workup

  1. custompurged with nitrogen
  2. temperatureAfter cooling to about room temperature
  3. filtrationfiltered through CELITE® (Celite Corp., Santa Barbara, Calif.)
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (hexanes:EtOAc, 5:1 to 3:1)

Sources & evidence

ORD record
ord-79f46b4d340e4ababfe93142f040a3ef
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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