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1,2-Dimethoxyethane → 6-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one

HRID 870648
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HRID 870648 반응식
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[O:16]=[C:17]1[C:26]2[C:21](=[CH:22][C:23](B(O)O)=[CH:24][CH:25]=2)[CH2:20][CH2:19][NH:18]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>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].O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:23]3[CH:22]=[C:21]4[C:26](=[CH:25][CH:24]=3)[C:17](=[O:16])[NH:18][CH2:19][CH2:20]4)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]
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참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 49835905(1-Oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)boronic acidHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

생성물 1

HCID 866963446-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one수율 44%

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매
HCID 962Water용매

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온도
160 °C

실험 절차

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (160 mg, 0.61 mmol), (1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)boronic acid (200 mg, 0.73 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (50 mg, 0.06 mmol), potassium phosphate (250 mg, 1.2 mmol), DME (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 160° C. for 360 s by microwave irradiation. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 mL). The combined organic layers were concentrated under reduced pressure to afford an oil that was purified by reverse phase HPLC to afford 6-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (90 mg, 44%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.11-8.20 (m, 2H), 7.94 (d, J=8.2 Hz, 1H), 7.84 (s, 1H), 7.57 (d, J=9.7 Hz, 1H), 6.67 (d, J=9.7 Hz, 1H), 3.50 (t, J=6.7 Hz, 2H), 3.34 (t, J=7.2 Hz, 2H), 3.00 (t, J=6.6 Hz, 2H), 1.60-1.75 (m, 2H), 1.36-1.50 (m, 2H), 0.95 (t, J=7.4 Hz, 3H); LCMS (ESI) m/e 336.2 [(M+H)+, calcd for C19H22N6O 336.2].

후처리

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2 mL)
  3. concentrationThe combined organic layers were concentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-66bc815b85ac429f92cb259ddb4de555
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08969565B2

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