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 1888556노트

반응식

HRID 1888556 반응식
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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 522689Potassium Fluoride용매

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온도
140 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0f4faad951884618803d91f527d1c302
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501765B2

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