Sodium Carbonate → methyl 2-(2-{[(tert-butoxycarbonyl)amino]methyl}-4-fluorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1714019Notes

Reaction equation

HRID 1714019 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.N1C2C(=CC=C(C(OC)=O)C=2)C=C1.C([O-])([O-])=O.[Na+].[Na+].[C:40]([O:44][C:45]([NH:47][CH2:48][C:49]1[CH:54]=[C:53]([F:55])[CH:52]=[CH:51][C:50]=1B(O)O)=[O:46])([CH3:43])([CH3:42])[CH3:41]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:40]([O:44][C:45]([NH:47][CH2:48][C:49]1[CH:54]=[C:53]([F:55])[CH:52]=[CH:51][C:50]=1[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2)=[O:46])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 36856242-(Aminomethyl)-4-fluorobenzeneboronic acid, N-BOC protectedHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 68510895methyl 2-(2-{[(tert-butoxycarbonyl)amino]methyl}-4-fluorophenyl)-3-cyclohexyl-1H-indole-6-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as described in published International patent application WO2004/087714, from commercially available methyl indole-6-carboxylate) in dioxane (0.07 M) was added 0.2 eq of bis(triphenylphosphine)palladium(II) dichloride at RT under a nitrogen atmosphere. Then aqueous Na2CO3 (2 M solution, 2 eq.) and [2-(N-tert-butoxycarbonyl-amino-methyl)-4-fluorophenyl]-boronic acid (2 eq.) were added and the reaction flask immersed in a preheated oil bath at 100° C. for 2 h. The reaction mixture was allowed to cool and filtered. The filtrate was diluted with DCM and the organic phase washed with H2O, brine and dried over Na2SO4 before being filtered and concentrated in vacuo. The crude material was purified by flash chromatography (1:9 EtOAc/PE) to afford the title compound as a solid (87%); MS (ES+) m/z 481 (M+H)+.

Workup

  1. temperatureto cool
  2. filtrationfiltered
  3. additionThe filtrate was diluted with DCM
  4. washthe organic phase washed with H2O, brine
  5. dry with materialdried over Na2SO4
  6. filtrationbefore being filtered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (1:9 EtOAc/PE)

Sources & evidence

ORD record
ord-2b2dcf27bfdf4c6fb59a9a2b02056f55
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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