4-(1-Piperidylmethyl)phenylboronic Acid → tert-Butyl-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate

HRID 1888571노트

반응식

HRID 1888571 반응식
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[N:16]=[CH:15][C:14]2[NH:13][C:12]3[N:17]=[CH:18][C:19](Br)=[CH:20][C:11]=3[C:10]=2[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[N:23]1([CH2:29][C:30]2[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl.O>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[N:16]=[CH:15][C:14]2[NH:13][C:12]3[N:17]=[CH:18][C:19]([C:33]4[CH:32]=[CH:31][C:30]([CH2:29][N:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)=[CH:35][CH:34]=4)=[CH:20][C:11]=3[C:10]=2[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 68346934tert-butyl-{3-Bromo-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate

생성물 1

HCID 68346928tert-Butyl-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate수율 30.1%

시약·촉매·용매 4

HCID 962Water용매HCID 6344Dichloromethane용매2회HCID 10796Cesium carbonate용매HCID 312751,4-Dioxane용매

실험 절차

A degassed mixture of tert-butyl-{3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-yl}-carbamate (229 mg, 0.631 mmol), 4-piperidin-1-ylmethyl-phenyl boronic acid (207 mg, 0.946 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (51.5 mg, 6.31 μmol, 10.0 mol %) in 1,4-dioxane (12.4 mL) and 2M aqueous cesium carbonate (1.32 mL) was heated under reflux for 5 h. The mixture was allowed to cool to room temperature, diluted with DCM and water, and filtered to remove the precipitate. The filtrate layers were separated and the aqueous phase was extracted with DCM, and the combined organic phase concentrated in vacuo. The resultant residue was dissolved in 20% methanol in DCM and absorbed onto silica gel for purification by flash chromatography (silica, 11 g column, Biotage, 1-20% methanol in DCM) to afford the title compound as a beige solid (86.9 mg, 30%). 1H NMR (DMSO-D6, 400 MHz): 11.96 (s, 1H), 9.55 (s, 1H), 8.99 (d, J=1.9 Hz, 1H), 8.88 (d, J=2.2 Hz, 1H), 8.57 (d, J=7.8 Hz, 2H), 7.80 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.35 (m, 4H), 1.55-1.45 (m, 4H), 1.52 (s, 9H), 1.39 (m, 2H). LCMS (Method D): RT=9.11 min, M+H+=458.

후처리

  1. temperaturewas heated
  2. temperatureunder reflux for 5 h
  3. filtrationfiltered
  4. customto remove the precipitate
  5. customThe filtrate layers were separated
  6. extractionthe aqueous phase was extracted with DCM
  7. concentrationthe combined organic phase concentrated in vacuo
  8. dissolutionThe resultant residue was dissolved in 20% methanol in DCM
  9. customabsorbed onto silica gel for purification by flash chromatography (silica, 11 g column, Biotage, 1-20% methanol in DCM)

출처 및 근거

ORD 기록
ord-540ccd2374284ed99b975454979d52f2
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501765B2

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