Potassium Carbonate → 1-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]cyclobutanecarboxylic acid

HRID 1054753노트

반응식

HRID 1054753 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=O)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([C:36]([OH:38])=[O:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([C:36]([OH:38])=[O:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 167699191-(4-Bromophenyl)cyclobutane-1-carboxylic acidHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

생성물 1

HCID 866987471-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]cyclobutanecarboxylic acid수율 63.6%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (200 mg, 0.80 mmol) in 1,4-dioxane (5 mL) and DMF (1 mL) was added N,N-dimethylformiminium chloride (250 mg, 2.00 mmol). The reaction mixture was sealed and stirred at room temperature for 10 minutes. To the resulting slurry was added 2 M aqueous potassium carbonate (2 mL, 4 mmol), 1-(4-bromophenyl)cyclobutanecarboxylic acid (255 mg, 1.00 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg). The reaction mixture was degassed with nitrogen, sealed, and heated to 90° C. for 30 minutes. The reaction was quenched with H2O (20 mL), then washed with ethyl acetate (3×20 mL). The combined organic phases were dried and concentrated in vacuo to give the title compound (180 mg, 63% yield) in crude form, which was used in the next step without further purification. 1H NMR (400 MHz, CD3OD) δ 9.90 (s, 1 H), 8.17 (s, 1 H), 8.13 (s, 1 H), 7.62-7.61 (m, 1 H), 7.48-7.45 (m, 2 H), 7.41-7.37 (m, 2 H), 2.86-2.79 (m, 2 H), 2.62-2.45 (m, 2 H), 2.05-2.01 (m, 2 H).

후처리

  1. customThe reaction mixture was sealed
  2. customThe reaction mixture was degassed with nitrogen
  3. customsealed
  4. temperatureheated to 90° C. for 30 minutes
  5. customThe reaction was quenched with H2O (20 mL)
  6. washwashed with ethyl acetate (3×20 mL)
  7. customThe combined organic phases were dried
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-5329e794e10e448ea49ca73cd6173e8c
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394285B2

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