Potassium Carbonate → 6-chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carbaldehyde

HRID 338225

반응식

HRID 338225 반응식
CC1(C)COB(B2OCC(C)(C)CO2)OC1.C([O-])(=O)C.[K+].Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]2([OH:33])[CH2:32][O:31][CH2:30]2)=[CH:25][CH:24]=1.Br[C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][C:43]=1[Cl:44])[NH:40][CH:39]=[C:38]2[CH:45]=[O:46].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].CCO.C1(C)C=CC=CC=1>[Cl:44][C:43]1[CH:42]=[C:41]2[C:37]([C:38]([CH:45]=[O:46])=[CH:39][NH:40]2)=[CH:36][C:35]=1[C:23]1[CH:28]=[CH:27][C:26]([C:29]2([OH:33])[CH2:32][O:31][CH2:30]2)=[CH:25][CH:24]=1

참가 물질

10

반응물 5

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 583823793-(4-Bromophenyl)oxetan-3-olHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehyde

생성물 1

HCID 866985766-chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carbaldehyde수율 35.5%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 702Ethanol용매HCID 1140Toluene용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

A mixture of 5,5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] (149.0 mg, 0.44 mmol), oven dried potassium acetate (173.0 mg, 1.75 mmol) and 3-(4-bromo-phenyl)-oxetan-3-ol (100.0 mg, 0.44 mmol) in 1,4-dioxane (2 mL) was degassed with N2 for 5 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (33.0 mg, 0.044 mmol) and subjected to microwave irradiation at 110° C. for 1 hour. The cooled reaction mixture was filtered through celite and concentrated in vacuo to give a black oil. To the dark oil was added 5-bromo-6-chloro-1H-indole-3-carbaldehyde (112.0 mg, 0.43 mmol), 2N aqueous potassium carbonate (0.4 mL, 0.80 mmol), toluene (1.5 mL) and EtOH (0.5 mL). The reaction mixture was degassed with N2 for 10 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (25.0 mg, 0.034 mmol), and heated in a pressure tube to 110° C. for 2 hours. The cooled reaction mixture was purified by flash chromatography (33-100% EtOAc/heptanes) to give a solid. The solid was triturated in MeOH and filtered to afford the title compound (50 mg, 35%) as a yellow solid. MS (ES+) 328.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 9.92 (s, 1H), 8.35 (s, 1H), 8.02 (s, 1H), 7.66 (d, J=9.4 Hz, 2H), 7.44 (d, J=8.2 Hz, 2H), 6.36 (s, 1H), 4.80-4.76 (m, 2H), 4.75-4.71 (m, 2H).

후처리

  1. customwas degassed with N2 for 5 minutes
  2. customirradiation at 110° C. for 1 hour
  3. customThe cooled reaction mixture
  4. filtrationwas filtered through celite and
  5. concentrationconcentrated in vacuo
  6. customto give a black oil
  7. customThe reaction mixture was degassed with N2 for 10 minutes
  8. customThe cooled reaction mixture
  9. customwas purified by flash chromatography (33-100% EtOAc/heptanes)
  10. customto give a solid
  11. customThe solid was triturated in MeOH
  12. filtrationfiltered

출처 및 근거

ORD 기록
ord-8152ea7e50ec43aea5cafab497fadaef
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889730B2

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