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Formaldehyde → 7-Fluoro-6-{6-[1-(1-methyl-azetidin-3-yl)-1H-pyrazol-4-yl]-imidazo[1,2-b]pyridazin-3-yl methyl}-quinoline

HRID 69183
ノート
印刷プレビュー

反応式

HRID 69183 の反応式
CO.[NH:3]1[CH2:6][CH:5]([N:7]2[CH:11]=[C:10]([C:12]3[CH:13]=[CH:14][C:15]4[N:16]([C:18]([CH2:21][C:22]5[CH:23]=[C:24]6[C:29](=[CH:30][C:31]=5[F:32])[N:28]=[CH:27][CH:26]=[CH:25]6)=[CH:19][N:20]=4)[N:17]=3)[CH:9]=[N:8]2)[CH2:4]1.C=O.[BH3-][C:36]#N.[Na+]>C(Cl)Cl.C(O)(=O)C>[F:32][C:31]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[CH2:21][C:18]1[N:16]2[N:17]=[C:12]([C:10]3[CH:9]=[N:8][N:7]([CH:5]4[CH2:4][N:3]([CH3:36])[CH2:6]4)[CH:11]=3)[CH:13]=[CH:14][C:15]2=[N:20][CH:19]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 686314996-[6-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-7-fluoro-quinoline

生成物 1

HCID 579174527-Fluoro-6-{6-[1-(1-methyl-azetidin-3-yl)-1H-pyrazol-4-yl]-imidazo[1,2-b]pyridazin-3-yl methyl}-quinoline

試薬・触媒・溶媒 2

HCID 176
Acetic Acid
溶媒
HCID 6344Dichloromethane溶媒

実験手順

A flask was charged with MeOH (1 mL). 6-[6-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-7-fluoro-quinoline (Stage 146.1, 26 mg, 0.065 mmol), formaldehyde (9.7 μL, 0.130 mmol) and NaBH3CN (20 mg, 0.325 mmol) were then added. The pH was adjusted to 5-6 with a drop of acetic acid and the RM was stirred at rt for 2 h. The mixture was then diluted with DCM, washed with NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with a 4 g RediSep® silica gel column, DCM/(DCM/MeOH 19:1)=100:0→0:100)). The residue crystallized in DCM. The solid was filtered off, and dissolved in EtOAc. The solution was washed again with NaHCO3, dried over Na2SO4, filtered and concentrated to afford the title compound as a foam (tR 2.93 min (conditions 3), MH+=414.1, 1H-NMR in DMSO-d6: 8.85 (m, 1H); 8.60 (s, 1H); 8.35 (m, 1H); 8.09 (m, 3H); 7.77 (m, 1H); 7.58 (m, 2H); 7.47 (m, 1H); 5.01 (m, 1H); 4.55 (s, 2H); 3.71 (m, 2H); 3.40 (m, 2H); 2.34 (s, 3H))

後処理

  1. washwashed with NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (CombiFlash® Companion System®
  6. customThe residue crystallized in DCM
  7. filtrationThe solid was filtered off
  8. dissolutiondissolved in EtOAc
  9. washThe solution was washed again with NaHCO3
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-d7db261cf07346c18aa7a6a50df3ea6b
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822468B2

反応ノート

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