4-Methylmorpholine → HCID 90113925, 화합물

HRID 2275901노트

반응식

HRID 2275901 반응식
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]

참가 물질

7

반응물 4

HCID 79724-Methylmorpholine2회HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11170953100868-68-62회HCID 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

생성물 1

HCID 90113925HCID 90113925, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 22392675Trifluoroacetic acid water용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-58837983373e41c7acc3fb3307997e4c
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09126998B2

반응 노트

불러오는 중…