1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine hydrochloride → 6-Chloro-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506018ノート

反応式

HRID 1506018 の反応式
Br[C:2]1[CH:15]=[N:14][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([Cl:13])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.Cl.CC1(C)C(C)(C)OB([C:25]2[CH:37]=[CH:36][C:28]([CH2:29][N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[CH:27][CH:26]=2)O1>C(#N)C.[F-].[K+]>[Cl:13][C:10]1[N:11]=[CH:12][C:7]2[NH:6][C:5]3[N:14]=[CH:15][C:2]([C:25]4[CH:26]=[CH:27][C:28]([CH2:29][N:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)=[CH:36][CH:37]=4)=[CH:3][C:4]=3[C:8]=2[CH:9]=1

参加物

5

反応物 2

HCID 467390331-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperidine hydrochlorideHCID 582664913-Bromo-6-chloro-9H-dipyrido[2,3-b;4',3'-d]pyrrole

生成物 1

HCID 582667236-Chloro-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole収率 66%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 522689Potassium Fluoride溶媒

反応条件

温度
140 °C

実験手順

A degassed mixture of 3-bromo-6-chloro-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (1.00 g, 3.55 mmol), 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-piperidine hydrochloride (1.24 g, 3.67 mmol) and 1,1′-[bis(diphenylphosphino) ferrocene]dichloro palladium(II) (0.29 g, 0.35 mmol) in acetonitrile (20 mL) and 2N aqueous potassium fluoride solution (10 mL) was heated under microwave irradiation at 140° C. for 30 minutes. The cooled reaction mixture was concentrated under reduced pressure and taken up in DCM/methanol and loaded onto an SCX-2 cartridge (20 g) which was then washed with methanol (50 mL) then 2N ammonia in methanol (50 mL). The combined basic fractions were concentrated in vacuo and the residue purified by flash chromatography (silica, 80 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as a pink solid (0.87 g, 66%). 1H NMR (DMSO-D6, 400 MHz): 12.38 (s, 1H), 9.03 (d, J=2.3 Hz, 1H), 8.95 (d, J=2.3 Hz, 1H), 8.71 (d, J=1.0 Hz, 1H), 8.38 (d, J=0.9 Hz, 1H), 7.75 (d, J=7.9 Hz, 2H), 7.44 (d, J=7.9 Hz, 2H), 3.49 (s, 2H), 2.39-2.33 (m, 4H), 1.56-1.48 (m, 4H), 1.45-1.37 (m, 2H). LCMS (Method B): RT=2.27 min, M+H+=377.

後処理

  1. customThe cooled reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. washwas then washed with methanol (50 mL)
  4. concentrationThe combined basic fractions were concentrated in vacuo
  5. customthe residue purified by flash chromatography (silica, 80 g column, ISCO, 0-10% methanol in DCM)

出典と根拠

ORDレコード
ord-5cf1912e91d043f5876a3083ea9dc5c8
出典データセット
uspto-grants-2015_12
特許番号
US09216980B2

反応ノート

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