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Isobutylamine → (Rac)-(6-isobutylamino-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol

HRID 69175
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HRID 69175 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].[CH2:25]([NH2:29])[CH:26]([CH3:28])[CH3:27]>CN1C(=O)CCC1.CC(OC)(C)C>[CH2:25]([NH:29][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1)[CH:26]([CH3:28])[CH3:27]
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참가 물질

6

반응물 3

HCID 6558IsobutylamineHCID 522689Potassium FluorideHCID 87524298(6-Chloroimidazo[1,2-b]pyridazin-3-yl)(quinolin-6-yl)methanol

생성물 1

HCID 44208574(Rac)-(6-isobutylamino-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol

시약·촉매·용매 2

HCID 13387N-methyl-2-pyrrolidone용매
HCID 15413
tert-Butyl methyl ether
용매

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온도
160 °C

실험 절차

(rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol (Stage 1.1, 80 mg, 0.257 mmol) and KF (30 mg, 0.515 mmol) were suspended in NMP (2 mL). Isobutylamine (129 μL, 1.287 mmol) was then added and the RM was stirred at 160° C. for 7 h. The mixture was diluted with TBME and washed with water (3×). The aqueous layer was then extracted with TBME (3×). The combined layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (Flashmaster) to afford the title compound as a yellow foam (tR 4.11 min (conditions 4), MH+=348.0, 1H-NMR in DMSO-d6: 8.86 (m, 1H); 8.32 (m, 1H); 8.02 (m, 1H); 7.94 (d, 1H); 7.80 (m, 1H); 7.61 (d, 1H); 7.51 (dd, 1H); 7.31 (s, 1H); 6.88 (t, 1Ht); 6.61 (d, 1H); 6.24 (m, 1H); 6.12 (d, 1H); 2.98 (m, 2H); 1.82 (m, 1H); 0.86 (m, 6H)).

후처리

  1. washwashed with water (3×)
  2. extractionThe aqueous layer was then extracted with TBME (3×)
  3. dry with materialThe combined layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (Flashmaster)

출처 및 근거

ORD 기록
ord-8783c27a2cc24dc389f649d4f5c1c640
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822468B2

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