Indole → HCID 50993869, compound

HRID 1784865Notes

Reaction equation

HRID 1784865 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH:20]=[CH:21][N:22]3[Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])[CH:5]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:7]=1.[N:37]1[CH:42]=[CH:41][CH:40]=[C:39](B(O)O)[CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+].N1C2C(=CC=CC=2)C=C1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC.C(O)C.C1(C)C=CC=CC=1>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:6]2[CH:5]=[C:4]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH:20]=[CH:21][N:22]4[Si:27]([CH:28]([CH3:29])[CH3:30])([CH:34]([CH3:35])[CH3:36])[CH:31]([CH3:32])[CH3:33])[CH:3]=[C:2]([C:39]3[CH:38]=[N:37][CH:42]=[CH:41][CH:40]=3)[CH:7]=2)=[CH:11][CH:12]=1

Participants

10

Reactant 4

HCID 798IndoleHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 50993867HCID 50993867, compound

Product 1

HCID 50993869HCID 50993869, compoundYield 46%

Reagents, catalysts & solvents 5

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 30 mL vial equipped with stir-bar was added 0.400 g (0.71 mmol) 4-[3-bromo-5-(4-methoxy-benzyloxy)-phenyl]-1-triisopropylsilanyl-1H-indole followed by 0.096 g (0.78 mmol) 3-pyridinyl boronic acid, 3 mL toluene, 3 mL ethanol, 0.71 mL 2 M aqueous sodium carbonate and 0.011 g (0.035 mmol) tetra n-butylammonium bromide. The starting indole did not dissolve, so 3 mL DME (ethylene glycol dimethyl ether) were added. The reaction mixture was degassed for 30 min by bubbling nitrogen into the mixture. Pd(PPh3)4 (0.018 g, 0.022 mmol) was added and the reaction mixture was heated to 100° C. overnight. The reaction mixture was cooled and filtered through Celite®, washing with ethyl acetate. The solvent was removed and the crude product was purified by preparative TLC (eluent: 30:70 ethyl acetate:hexane) to give 0.184 g of 4-[3-(4-methoxy-benzyloxy)-5-pyridin-3-yl-phenyl]-1-triisopropylsilanyl-1H-indole. This compound was deprotected as described in Example 34. 1H NMR (400 MHz, CDCl3): δ 10.07 (d, J=2.1 Hz, 1H), 9.74 (dd, J=4.9, 1.3 Hz, 1H), 9.30 (dt, J=4.9, 2.6 Hz, 1H), 8.70 (q, J=4.3 Hz, 1H), 8.65-8.61 (m, 2H), 8.53 (d, J=3.3 Hz, 1H), 8.45-8.36 (m, 3H), 8.29 (t, J=1.9 Hz, 1H), 7.89 (d, J=3.1 Hz, 1H).

Workup

  1. customTo a 30 mL vial equipped with stir-bar
  2. customThe reaction mixture was degassed for 30 min
  3. customby bubbling nitrogen into the mixture
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered through Celite®
  6. washwashing with ethyl acetate
  7. customThe solvent was removed
  8. customthe crude product was purified by preparative TLC (eluent: 30:70 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-9bc5d12d03d845a8b0bc4a3b31c4ecde
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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