1,2-Dichloroethane → (S)-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 1517824Notes

Reaction equation

HRID 1517824 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].C(Cl)CCl>CN(C1C=CN=CC=1)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

6

Reactant 3

HCID 111,2-DichloroethaneHCID 673N,N-DimethylglycineHCID 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 59491008(S)-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 61.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of (S)—N-(3-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl-1-(2-hydro-xylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (0.54 g, 1 mmol), N,N-dimethylglycine (0.206 g, 2 mmol, Alfa) and DMAP (0.244 g, 2 mmol, Aladdin) in 15 mL of CH2Cl2 at 0° C. was added EDC solid (0.575 g, 3 mmol, Aladdin) in portions. The mixture was continued to stir at 0° C. for 2 hrs, then the reaction mixture was warmed up to room temperature and stirred at rt for 20 hrs. The reaction mixture was diluted with 100 mL of CH2Cl2 and washed with 0.1 N HCl (10 mL×2), followed by saturated NaHCO3 (20 mL×2) and water (20 mL×8), and the aqueous phase was extracted with EtOAc(15 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc) to afford the title compound as a yellow solid (0.387 g, 61.6%).

Workup

  1. temperaturethe reaction mixture was warmed up to room temperature
  2. stirringstirred at rt for 20 hrs
  3. washwashed with 0.1 N HCl (10 mL×2)
  4. extractionthe aqueous phase was extracted with EtOAc(15 mL×2)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-8b727616d1764a9a8a0708bfa5201f2b
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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