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 882306Notes

Reaction equation

HRID 882306 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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

Workup

  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)

Sources & evidence

ORD record
ord-452c7729bcd44ffb8437760b16035da9
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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