1,2-Dichloroethane → HCID 66669894, compound

HRID 1517823Notes

Reaction equation

HRID 1517823 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][C@@H: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.[C:41]([NH:48][CH2:49][C:50](O)=[O:51])([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:44]([O:43][C:41]([NH:48][CH2:49][C:50]([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:51])=[O:42])([CH3:47])([CH3:46])[CH3:45]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 78288N-(tert-butoxycarbonyl)glycineHCID 24901694N-{3-fluoro-4-[(7-methoxyquinolin-4-yl)oxy]phenyl}-1-[(2S)-2-hydroxypropyl]-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 66669894HCID 66669894, compoundYield 113.4%

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-hydroxylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (1.0 g, 1.84 mmol), N-Boc-glycine (0.644 g, 3.68 mmol, ABCR) and DMAP (0.45 g, 3.68 mmol, Aladdin) in 12 mL of CH2Cl2 at 0° C. was added EDC solid (1.0582 g, 5.52 mmol, Aladdin) in portions. After stirring at 0° C. for 2 hrs, the reaction mixture was warmed up to room temperature and continued to stir overnight. The reaction mixture was diluted with CH2Cl2 (100 mL), and the result solution was washed with 0.1 N HCl (10 mL×2), followed by saturated NaHCO3 (10 mL×2) and water (20 mL), the aqueous phase was extracted with EtOAc (15 mL×3). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc:hexane=2:1) to give the desired compound as a yellow solid (1.46 g, 70.1%).

Workup

  1. temperaturethe reaction mixture was warmed up to room temperature
  2. stirringto stir overnight
  3. washthe result solution was washed with 0.1 N HCl (10 mL×2)
  4. extractionthe aqueous phase was extracted with EtOAc (15 mL×3)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (EtOAc:hexane=2:1)

Sources & evidence

ORD record
ord-69a346194446405899d2e6ed2de09737
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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