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

HRID 1714019노트

반응식

HRID 1714019 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-2b2dcf27bfdf4c6fb59a9a2b02056f55
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07795247B2

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