Triethylamine → 2,2-difluoro-N'-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide

HRID 40347ノート

反応式

HRID 40347 の反応式
[F:1][C:2]([F:18])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][C:10]([O:16][CH3:17])=[CH:9]2)[C:3]([OH:5])=O.S(Cl)(Cl)=O.C(N(CC)CC)C.[F:30][C:31]1[C:32]([NH:43][NH2:44])=[N:33][CH:34]=[C:35]([C:37]2[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=2)[CH:36]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl.CO.CN(C=O)C>[F:18][C:2]([F:1])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][C:10]([O:16][CH3:17])=[CH:9]2)[C:3]([NH:44][NH:43][C:32]1[C:31]([F:30])=[CH:36][C:35]([C:37]2[CH:38]=[N:39][N:40]([CH3:42])[CH:41]=2)=[CH:34][N:33]=1)=[O:5]

参加物

9

反応物 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 576912392,2-Difluoro-2-(3-methoxyquinolin-6-yl)acetic acidHCID 675032383-fluoro-2-hydrazinyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine

生成物 1

HCID 576913272,2-difluoro-N'-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide収率 33.1%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

A round bottom flask was charged with 2,2-difluoro-2-(3-methoxyquinolin-6-yl)acetic acid (389 mg, 1536 μmol) and DMF (8 mL). The solution was cooled to 0 C, thionyl chloride (224 μl, 3073 mmol), was added and the resulting solution was maintained 1 h at 0° C. Then, triethylamine (641 μl , 4609 μmol) was added via syringe, followed by 1-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)hydrazine (382 mg, 1844 μmol) and 4-(dimethylamino)pyridine (18.8 mg, 154 μmol); both added as solids. The heterogeneous solution was stirred at 0° C. for 1 h, then allowed to warm to rt and stir for 18 h. The mixture was quenched with saturated aqueous NaHCO3 (50 mL) and the resulting mixture was extracted with CH2Cl2 (3×50 mL). The combined organic layers were concentrated (heating to 50° C.) and the residue purified by SiO2 chromatography solvent system: CH2Cl2:MeOH 99%:1% gradient 90:10 CH2Cl2 to yield 2,2-difluoro-N′-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(3-methoxyquinolin-6-yl)acetohydrazide (225 mg, 33.1% yield) as a brown amorphous solid.

後処理

  1. additionwas added
  2. additionboth added as solids
  3. temperatureto warm to rt
  4. stirringstir for 18 h
  5. customThe mixture was quenched with saturated aqueous NaHCO3 (50 mL)
  6. extractionthe resulting mixture was extracted with CH2Cl2 (3×50 mL)
  7. concentrationThe combined organic layers were concentrated
  8. temperature(heating to 50° C.)
  9. customthe residue purified by SiO2 chromatography solvent system

出典と根拠

ORDレコード
ord-1d305321ce7047e38c89c25e2dde3e1f
出典データセット
uspto-grants-2013_09
特許番号
US08524900B2

反応ノート

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