1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (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-(tert-butoxycarbonylamino)acetate

HRID 1517846Notes

Reaction equation

HRID 1517846 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:21])[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:22]([O:26][C:27]([NH:29][CH2:30][C:31]([O:33][C@H:34]([CH3:52])[CH2:35][N:36]1[C:40]([CH3:41])=[C:39]([C:42](O)=[O:43])[C:38](=[O:45])[N:37]1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[C:22]([O:26][C:27]([NH:29][CH2:30][C:31]([O:33][C@H:34]([CH3:52])[CH2:35][N:36]1[C:40]([CH3:41])=[C:39]([C:42](=[O:43])[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:38](=[O:45])[N:37]1[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:32])=[O:28])([CH3:23])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 595983543-Fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamineHCID 66670730(R)-1-(2-(2-(tert-butoxycarbonylamino)acetoxy)propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid

Product 1

HCID 66670684(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-(tert-butoxycarbonylamino)acetateYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine (399 mg, 1.38 mmol), (R)-1-(2-(2-(tert-butoxycarbonylamino)acetoxy)propyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (500 mg, 1.15 mmol) in dry CH2Cl2 (5 mL) was added EDCI (264 mg, 1.38 mmol) and HOAT (32 mg, 0.23 mmol). The mixture reaction was refluxed for 3 h. The reaction mixture was then concentrated in vacuo and the residue was purified by a silica gel column chromatography (100% EtOAc) to give the title compound as a white solid (610 mg, 76%).

Workup

  1. customThe mixture reaction
  2. temperaturewas refluxed for 3 h
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. customthe residue was purified by a silica gel column chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-8038d7febff944509b62687669be47f3
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

Loading…