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

HRID 2190101노트

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HRID 2190101 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.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.[CH2:54]([N:61]1[CH2:66][CH2:65][C:64]2([C:74]3[C:69](=[CH:70][CH:71]=[CH:72][C:73]=3[CH:75]([OH:77])[CH3:76])[NH:68][CH2:67]2)[CH2:63][CH2:62]1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[CH2:54]([N:61]1[CH2:66][CH2:65][C:64]2([C:74]3[C:69](=[CH:70][CH:71]=[CH:72][C:73]=3[CH:75]([OH:77])[CH3:76])[N:68]([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)[CH2:67]2)[CH2:63][CH2:62]1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59670769(R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineHCID 698103581-(1'-Benzylspiro[indoline-3,4'-piperidine]-4-yl)ethanol

생성물 1

HCID 687620901-(1'-benzyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)ethanol수율 31.2%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

A flask was charged with Pd(OAc)2 (0.0027 g, 0.012 mmol) and Xantphos (0.010 g, 0.018 mmol) and purged with nitrogen. The flask was then charged with (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (0.022 g, 0.13 mmol), 1-(1′-benzylspiro[indoline-3,4′-piperidine]-4-yl)ethanol (0.047 g, 0.12 mmol), Cs2CO3 (0.058 g, 0.18 mmol), and toluene (0.6 mL) The reaction was purged with nitrogen and heated to 100° C. for 3 hours. Additional (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine was added, and the reaction was heated at 100° C. for an additional 4 hours and then stirred at room temperature overnight. The reaction was filtered through GFF and concentrated under reduced pressure. The crude residue was purified by column chromatography (5% MeOH/DCM, then 5% 7N NH4 in MeOH/DCM) to yield 1-(1′-benzyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)ethanol (0.017 g, 31%). LCMS (APCI+) m/z 455.2 [M+H]+; Rt=3.18 min.

후처리

  1. custompurged with nitrogen
  2. customwas purged with nitrogen
  3. additionAdditional (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine was added
  4. temperaturethe reaction was heated at 100° C. for an additional 4 hours
  5. filtrationThe reaction was filtered through GFF
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by column chromatography (5% MeOH/DCM

출처 및 근거

ORD 기록
ord-6abadea0d2b549b093814ff9e2d5f8e5
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324221B2

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