N,N-Dimethylglycine → (R)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-(dimethylamino)acetate

HRID 1517847Notes

Reaction equation

HRID 1517847 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:21][C:22]([C:24]2[C:25](=[O:40])[N:26]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:27]([CH2:30][CH:31]([OH:33])[CH3:32])[C:28]=2[CH3:29])=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[CH3:41][N:42]([CH3:47])[CH2:43][C:44](O)=[O:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C.C(Cl)Cl>[CH3:41][N:42]([CH3:47])[CH2:43][C:44]([O:33][C@H:31]([CH3:32])[CH2:30][N:27]1[C:28]([CH3:29])=[C:24]([C:22](=[O:23])[NH:21][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=4)[N:12]=[CH:11][CH:10]=3)=[C:2]([F:1])[CH:3]=2)[C:25](=[O:40])[N:26]1[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:45]

Participants

7

Reactant 3

HCID 673N,N-DimethylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595983963-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 46938003(R)-1-(4-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)phenylcarbamoyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydropyrazol-1-yl)propan-2-yl 2-(dimethylamino)acetateYield 90.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (R)—N-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydrox-ylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1.08 g, 2.0 mmol), N,N-dimethylglycine (0.516 g, 5 mmol Alfa Aesar), HATU (1.902 g. 5 mmol) and DMAP (62.5 mg, 0.5 mmol, Aladdin) was added TEA (1.012 g, 10 mmol) in DMF (12.5 mL) under nitrogen atmosphere at 0° C. The reaction was stirred at 0° C. for 2 hrs, and then warmed up to room temperature and continued to stir overnight. The reaction was diluted with 100 mL of CH2Cl2. The resulted solution was washed with 0.1 N HCl (10 mL×2), saturated NaHCO3 (20 mL×2) and followed by water (20 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc/MeOH=2/1) to give the title compound as a yellow solid (1.1367 g, 84%).

Workup

  1. temperaturewarmed up to room temperature
  2. stirringto stir overnight
  3. washThe resulted solution was washed with 0.1 N HCl (10 mL×2), saturated NaHCO3 (20 mL×2)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (EtOAc/MeOH=2/1)

Sources & evidence

ORD record
ord-687684de45ed45958eefa926352fce32
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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