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Acetonitrile → butyl-[3-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine

HRID 870642
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HRID 870642 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.[NH:16]1[CH:20]=[C:19](B(O)O)[CH:18]=[N:17]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(#N)C>Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:19]3[CH:20]=[N:16][NH:17][CH:18]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]
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참가 물질

7

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HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 177502781H-Pyrazole-4-boronic acidHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

생성물 1

HCID 136378620butyl-[3-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine수율 63.3%

시약·촉매·용매 2

HCID 178418903
HCID 178418903, 화합물
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 (100 mg, 0.37 mmol), (1H-pyrazol-4-yl)boronic acid (90 mg, 0.45 mmol), dichloro-bis(triphenylphosphino) palladium (II) (15 mg, 0.021 mmol), potassium phosphate (80 mg, 0.56 mmol), acetonitrile (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 160° C. for 1000 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 butyl-[3-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine (60 mg, 62%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67 (s, 1H), 7.59 (d, J=9.6 Hz, 1H), 6.67 (d, J=9.6 Hz, 1H), 3.44 (t, J=7.1 Hz, 1H), 1.70-1.80 (m, 1H), 1.46-1.59 (m, 1H), 1.03 (t, J=7.3 Hz, 1H); LCMS (ESI) m/e 257.3 [(M+H)+, calcd for C13H17N6 257.1].

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-fc5fa78766ee41edb5c063fc66ae3d99
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08969565B2

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