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 2174093노트

반응식

HRID 2174093 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 2724682Lithium diisopropylamide용매

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온도
-78 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f5879676d2f54cd0a6efc36d96a18b4c
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09056874B2

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