1,2-Dichloroethane → HCID 68739076, compound

HRID 1517884Notes

Reaction equation

HRID 1517884 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]2[C:26](=[O:41])[N:27]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:28]([CH2:31][C@H:32]([OH:34])[CH3:33])[C:29]=2[CH3:30])=[O:24])=[CH:18][C:17]=1[F:42].[C:43]([NH:50][CH2:51][C:52](O)=[O:53])([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]2[C:26](=[O:41])[N:27]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:28]([CH2:31][C@H:32]([O:34][C:52](=[O:53])[CH2:51][NH:50][C:43]([O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[O:44])[CH3:33])[C:29]=2[CH3:30])=[O:24])=[CH:18][C:17]=1[F:42]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 78288N-(tert-butoxycarbonyl)glycineHCID 59598358(R)-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 68739076HCID 68739076, compoundYield 95.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (R)—N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-1-(2-hydroxypropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (2.0 g, 3.5 mmol), N-Boc-glycine (1.23 g, 7.0 mmol) and DMAP (0.86 g, 7.0 mmol) in CH2Cl2 (45 mL) at 0° C. was added EDC solid (2.02 g, 10.5 mmol) in portions. The reaction mixture was stirred at 0° C. for 2 h, then warmed up to rt and continued to stir overnight. The reaction mixture was diluted with CH2Cl2 (50 mL), and washed with 0.5 N HCl aqueous (20 mL), saturated NaHCO3 (20 mL), and followed by brine (20 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (n-hexane/ethyl acetate at the ratio of 1:1 to 1:8) to give the title compound as a white powder (2.43 g, 95.2%).

Workup

  1. temperaturewarmed up to rt
  2. stirringto stir overnight
  3. washwashed with 0.5 N HCl aqueous (20 mL), saturated NaHCO3 (20 mL)
  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 (n-hexane/ethyl acetate at the ratio of 1:1 to 1:8)

Sources & evidence

ORD record
ord-e0b59e63b4114ffda3a14c65da3dc87a
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

Loading…