Potassium Carbonate → 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde

HRID 338406

반응식

HRID 338406 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:27]=[N:28][C:29]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:30][CH:31]=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:27]=[N:28][C:29]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:30][CH:31]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 51443624-(5-Bromopyrimidin-2-yl)morpholineHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

생성물 1

HCID 866987436-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde수율 79.4%

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 (154 mg, 0.584 mmol) in anhydrous 1,4-dioxane (5 mL) and DMF (1 mL) was added N,N-dimethylformiminium chloride (150 mg, 1.17 mmol). The reaction mixture was stirred at room temperature for 20 minutes, then treated with 2M aqueous potassium carbonate (400 mg, 2.90 mmol), 4-(5-bromopyrimidin-2-yl)morpholine (145 mg, 0.594 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg, 0.068 mmol). The reaction was degassed with nitrogen for 2 minutes and heated to 90° C. for 30 minutes. The cooled reaction mixture was concentrated in vacuo and purified by column chromatography on silica gel (petroleum ether/EtOAc=1:4) to afford 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (159 mg, 79.4% yield) as an yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 10.01 (s, 1H), 8.55 (s, 2H), 8.46 (s, 1H), 8.12 (s, 1H), 7.79 (s, 1H), 3.84 (m, 4H), 3.77 (m, 4H).

후처리

  1. customThe reaction was degassed with nitrogen for 2 minutes
  2. temperatureheated to 90° C. for 30 minutes
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. custompurified by column chromatography on silica gel (petroleum ether/EtOAc=1:4)

출처 및 근거

ORD 기록
ord-866b38e1c23d41cea2df8f36567be2ca
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889730B2

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