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 2174093Notes

Reaction equation

HRID 2174093 reaction equation
[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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 2724682Lithium diisopropylamideSolvent

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f5879676d2f54cd0a6efc36d96a18b4c
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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