Sodium t-butoxide → 1-(7-Fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

HRID 1618555ノート

反応式

HRID 1618555 の反応式
C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].[O:41]1[CH2:46][CH2:45][N:44]([C:47]2[CH:52]=[C:51]3[NH:53][CH2:54][C:55]4([CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[C:50]3=[CH:49][CH:48]=2)[CH2:43][CH2:42]1.Cl[C:62]1[C:71]2[C:66](=[CH:67][C:68]([F:72])=[CH:69][CH:70]=2)[N:65]=[C:64]([C:73]2[CH:78]=[CH:77][CH:76]=[C:75]([S:79]([CH3:82])(=[O:81])=[O:80])[CH:74]=2)[C:63]=1[CH3:83]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:72][C:68]1[CH:67]=[C:66]2[C:71]([C:62]([N:53]3[C:51]4[C:50](=[CH:49][CH:48]=[C:47]([N:44]5[CH2:43][CH2:42][O:41][CH2:46][CH2:45]5)[CH:52]=4)[C:55]4([CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[CH2:54]3)=[C:63]([CH3:83])[C:64]([C:73]3[CH:78]=[CH:77][CH:76]=[C:75]([S:79]([CH3:82])(=[O:80])=[O:81])[CH:74]=3)=[N:65]2)=[CH:70][CH:69]=1

参加物

7

反応物 4

HCID 23676156Sodium t-butoxideHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]HCID 672853434-Chloro-7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)quinolineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

生成物 1

HCID 509387191-(7-Fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

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 mixture of 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (24.5 mg, 0.051 mmol), Pd2dba3 (23.6 mg, 0.026 mmol), sodium tert-butoxide (49.5 mg, 0.52 mmol), 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (47.1 mg, 0.17 mmol) (described herein), and 4-chloro-7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)quinoline (60 mg, 0.17 mmol) (described herein) in toluene (1.7 mL) was stirred at 100° C. for 60 min, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine, then the organic layer dried (MgSO4) and concentrated. Column chromatography afforded 1-(7-fluoro-3-methyl-2-(3-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran] as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.24 (1H, d, J=2.0 Hz), 8.07 (1H, d), 7.96 (1H, d), 7.76 (3H, m), 7.31 (1H, m), 7.15 (1H, d, J=8.2 Hz), 6.36 (1H, d), 5.59 (1H, s), 4.01-4.10 (2H, m), 3.91-4.01 (2H, m), 3.69-3.82 (4H, m), 3.51-3.63 (2H, m), 3.11-3.19 (3H, m), 2.97 (4H, d, J=4.7 Hz), 2.25-2.33 (3H, m), 2.10-2.24 (2H, m), 1.89 (1H, d), 1.80 (1H, d). Mass Spectrum (ESI) m/e=588 (M+1).

後処理

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. washwashed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine
  4. dry with materialthe organic layer dried (MgSO4)
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-6bdf1b68574a4cee9daebbd92eb5d40d
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

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