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 1888571ノート

反応式

HRID 1888571 の反応式
[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]

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 10796Cesium carbonate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-540ccd2374284ed99b975454979d52f2
出典データセット
uspto-grants-2013_08
特許番号
US08501765B2

反応ノート

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