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 529153ノート

反応式

HRID 529153 の反応式
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

参加物

7

反応物 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

生成物 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)methylcarbamate収率 69.3%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ff768b6fe67b488ba9fd0048379afd23
出典データセット
uspto-grants-2016_05
特許番号
US09346805B2

反応ノート

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