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 529153노트

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HRID 529153 반응식
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

참가 물질

7

반응물 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

생성물 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)methylcarbamate수율 69.3%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ff768b6fe67b488ba9fd0048379afd23
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346805B2

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