4-Methylmorpholine → HCID 90113925、化合物

HRID 2275901ノート

反応式

HRID 2275901 の反応式
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CN1CCOCC1.[CH3:30][C:31]([NH2:37])([CH2:34][CH2:35][CH3:36])[CH2:32][NH2:33].[Cl:38][C:39]1[CH:40]=[C:41]([O:52][CH2:53][C:54]2[C:59]([F:60])=[CH:58][CH:57]=[CH:56][C:55]=2[F:61])[C:42]2[N:43]([C:45]([C:49](O)=[O:50])=[C:46]([CH3:48])[N:47]=2)[CH:44]=1>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:37][C:31]([CH3:30])([CH2:34][CH2:35][CH3:36])[CH2:32][NH:33][C:49]([C:45]1[N:43]2[CH:44]=[C:39]([Cl:38])[CH:40]=[C:41]([O:52][CH2:53][C:54]3[C:55]([F:61])=[CH:56][CH:57]=[CH:58][C:59]=3[F:60])[C:42]2=[N:47][C:46]=1[CH3:48])=[O:50]

参加物

7

反応物 4

HCID 79724-Methylmorpholine2 回HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11170953100868-68-62 回HCID 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

生成物 1

HCID 90113925HCID 90113925、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 22392675Trifluoroacetic acid water溶媒

実験手順

191 mg (0.62 mmol) of TBTU and 0.25 ml (2.27 mmol) of 4-methylmorpholine and 72 mg (0.62 mmol) of rac-2-methylpentane-1,2-diamine were added to 200 mg (0.57 mmol) of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 16A in DMF (2.0 ml), and the reaction mixture was stirred at RT overnight. 36 mg (0.31 mmol) of rac-2-methylpentane-1,2-diamine and 0.06 ml (0.57 mmol) of 4-methylmorpholine were then added, and stirring was continued at RT overnight. The mixture was diluted with water/TFA and purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fraction was concentrated. Saturated aqueous sodium bicarbonate solution was added to the residue, and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered off and concentrated. The residue was purified by silica gel chromatography (dichloromethane/methanol: 10:1, then dichloromethane/2N ammonia in methanol 20:1). This gave 189 mg (73% of theory, purity 99%) of the target compound.

後処理

  1. stirringstirring
  2. waitwas continued at RT overnight
  3. custompurified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  4. concentrationThe product fraction was concentrated
  5. additionSaturated aqueous sodium bicarbonate solution was added to the residue
  6. extractionthe mixture was extracted three times with dichloromethane
  7. dry with materialThe combined organic phases were dried over sodium sulphate
  8. filtrationfiltered off
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (dichloromethane/methanol

出典と根拠

ORDレコード
ord-58837983373e41c7acc3fb3307997e4c
出典データセット
uspto-grants-2015_09
特許番号
US09126998B2

反応ノート

読み込み中…