Morpholine → 1-((2S,4R)-2-methyl-4-(pyridin-2-ylamino)-6-(4-(pyrrolidine-1-carbonyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)ethanone formate

HRID 882306노트

반응식

HRID 882306 반응식
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([O-:20])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[O:3])[CH3:2].[Li+].CN(C(ON1N=NC2[CH:43]=[CH:44][CH:45]=[N:46][C:41]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N1CCCC1.N1CCOCC1>CN(C=O)C.O>[CH:18]([OH:20])=[O:19].[CH3:30][C@H:5]1[CH2:6][C@@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([N:46]4[CH2:45][CH2:44][CH2:43][CH2:41]4)=[O:19])=[CH:21][CH:22]=3)[CH:9]=2)[N:4]1[C:1](=[O:3])[CH3:2]

참가 물질

8

반응물 5

HCID 8083MorpholineHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70976493lithium 4-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

생성물 1

HCID 714686451-((2S,4R)-2-methyl-4-(pyridin-2-ylamino)-6-(4-(pyrrolidine-1-carbonyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)ethanone formate수율 12%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

Crude lithium 4-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)benzoate for a preparation see Intermediate 58) (40 mg) and HATU (41 mg, 0.108 mmol) in DMF (0.5 mL) were treated with DIPEA (51.2 μL, 0.294 mmol) and the mixture shaken and sonicated until a solution was formed (<2 min). This solution was added to pyrrolidine (16 μL, 0.192 mmol), the mixture briefly shaken then left to stand at room temperature for 2 h. A further portion of morpholine (32 μL, 0.384 mmol) was added and the mixture left to stand overnight. The mixture was diluted with water and extracted three times with DCM. The combined organic layers were dried by passing through a hydrophobic frit and concentrated in vacuo to give a residue. The residue was purified by MDAP (formate) to give 1-((2S,4R)-2-methyl-4-(pyridin-2-ylamino)-6-(4-(pyrrolidine-1-carbonyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)ethanone formate (23 mg, 0.046 mmol, 12%) as a pale pink glass. LCMS: (Formate, 2 min), Rt=0.70 min, MH+455

후처리

  1. customsonicated until a solution
  2. customwas formed (<2 min)
  3. stirringthe mixture briefly shaken
  4. waitthen left
  5. waitthe mixture left
  6. waitto stand overnight
  7. extractionextracted three times with DCM
  8. customThe combined organic layers were dried
  9. concentrationconcentrated in vacuo
  10. customto give a residue
  11. customThe residue was purified by MDAP (formate)

출처 및 근거

ORD 기록
ord-452c7729bcd44ffb8437760b16035da9
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993554B2

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