Diisopropylethylamine → 5-Cyclopropyl-6-cyclopropylmethoxy-nicotinic acid N'-(4-fluoro-phenyl)-N'-methyl-hydrazide

HRID 240747

反応式

HRID 240747 の反応式
[CH:1]1([C:4]2[C:5]([O:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[N:6][CH:7]=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[F:50][C:51]1[CH:56]=[CH:55][C:54]([N:57]([CH3:59])[NH2:58])=[CH:53][CH:52]=1>CN(C=O)C.O1CCCC1>[F:50][C:51]1[CH:56]=[CH:55][C:54]([N:57]([CH3:59])[NH:58][C:9](=[O:11])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[C:5]([O:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[N:6][CH:7]=2)=[CH:53][CH:52]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712939865-Cyclopropyl-6-cyclopropylmethoxy-nicotinic acidHCID 866781051-(4-Fluorophenyl)-1-methylhydrazine hydrochloride

生成物 1

HCID 712943115-Cyclopropyl-6-cyclopropylmethoxy-nicotinic acid N'-(4-fluoro-phenyl)-N'-methyl-hydrazide収率 97.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

In a 10 mL two-necked flask, the above prepared 5-cyclopropyl-6-cyclopropylmethoxy-nicotinic acid (70 mg, 300 μmol, Eq: 1.00) was combined with tetrahydrofuran (3 mL) and DMF (1 mL) to give a colorless solution. TBTU (145 mg, 450 μmol, Eq: 1.5) and N,N-diisopropylethylamine (194 mg, 262 μl, 1.5 mmol, Eq: 5) were added and the reaction mixture stirred for 10 min at rt, before 1-(4-fluorophenyl)-1-methylhydrazine hydrochloride (63.6 mg, 360 μmol, Eq: 1.2, CAN 1978-54-7) was added and the reaction mixture kept overnight at rt. The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl solution, combined, dried over Na2SO4 and concentrated in vacuo. The crude material was eventually purified by flash chromatography (silica gel, 20 g, 15% to 40% EtOAc in heptane) to provide 104 mg of the title product as colorless oil; MS (EI) 354.6 (M−H)−.

後処理

  1. customto give a colorless solution
  2. additionwas added
  3. customThe reaction mixture was quenched with 1 M HCl (10 mL)
  4. extractionextracted with EtOAc (2×20 mL)
  5. washThe organic layers were washed with 1 M NaOH
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was eventually purified by flash chromatography (silica gel, 20 g, 15% to 40% EtOAc in heptane)

出典と根拠

ORDレコード
ord-5c16ff33277747f4b8094a70b40f75ea
出典データセット
uspto-grants-2014_02
特許番号
US08648099B2

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