Tetrahydrofuran heptane ethylbenzol → tert-Butyl-4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174093ノート

反応式

HRID 2174093 の反応式
[CH3:1][Si:2]([CH3:19])([CH3:18])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=2)[CH:9]=[CH:8]1.CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.[CH:40]([C:42]1[C:50]([O:51][CH3:52])=[CH:49][C:48]([CH3:53])=[C:47]2[C:43]=1[CH:44]=[CH:45][N:46]2[C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])=[O:41]>C1COCC1.[Li+].CC([N-]C(C)C)C>[C:57]([O:56][C:54]([N:46]1[C:47]2[C:43](=[C:42]([CH:40]([C:8]3[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:19])([CH3:18])[CH3:1])[C:15]4[C:10]([CH:9]=3)=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=4)[OH:41])[C:50]([O:51][CH3:52])=[CH:49][C:48]=2[CH3:53])[CH:44]=[CH:45]1)=[O:55])([CH3:60])([CH3:58])[CH3:59]

参加物

6

反応物 3

HCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylateHCID 867017281-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-6-carbonitrile

生成物 1

HCID 86701729tert-Butyl-4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 2724682Lithium diisopropylamide溶媒

反応条件

温度
-78 °C

実験手順

To a solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-6-carbonitrile (424 mg, 1.55 mmol) in THF (0.7 mL), 1.8 M LDA in heptane/THF/ethylbenzene (139 mg, 1.29 mmol) was added at −78° C. The reaction was stirred at −78° C. for 30 minutes. tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (250 mg, 0.86 mmol) in THF (0.7 mL) was added at −78° C. The reaction was quenched with MeOH and then a saturated aq. ammonium chloride solution. The mixture was then diluted with EtOAc and the organic layer was removed, dried over MgSO4, filtered and concentrated. The resulting residue was purified via flash chromatography (0-40% EtOAc:heptanes) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) d ppm 8.06 (s, 1H) 7.61 (d, J=8.34 Hz, 1H) 7.51 (d, J=3.79 Hz, 1H) 7.34 (dd, J=8.21, 1.39 Hz, 1H) 6.91 (s, 1H) 6.79 (d, J=3.79 Hz, 1H) 6.63-6.71 (m, 1H) 6.20 (s, 1H) 6.09 (d, J=4.80 Hz, 1H) 5.57-5.74 (m, 2H) 3.81 (s, 3H) 3.40 (ddd, J=9.22, 6.82, 2.15 Hz, 2H) 2.55 (s, 3H) 1.50-1.63 (m, 9H) 0.78 (td, J=9.28, 6.95 Hz, 2H) −0.13-−0.09 (m, 9H).

後処理

  1. customThe reaction was quenched with MeOH
  2. additionThe mixture was then diluted with EtOAc
  3. customthe organic layer was removed
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified via flash chromatography (0-40% EtOAc:heptanes)

出典と根拠

ORDレコード
ord-f5879676d2f54cd0a6efc36d96a18b4c
出典データセット
uspto-grants-2015_06
特許番号
US09056874B2

反応ノート

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