Dicyclohexylcarbodiimide → 1-(3-(4-(4-(2,3-dimethyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)quinolin-7-yloxy)propyl)cyclopropyl 2-(tert-but-oxycarbonylamino)acetate

HRID 1517869Notes

Reaction equation

HRID 1517869 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:27][C:28]([C:30]2[C:31](=[O:43])[N:32]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:33]([CH3:36])[C:34]=2[CH3:35])=[O:29])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH2:22][C:23]3([OH:26])[CH2:25][CH2:24]3)=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[C:44]([NH:51][CH2:52][C:53](O)=[O:54])([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl>[C:47]([O:46][C:44]([NH:51][CH2:52][C:53]([O:26][C:23]1([CH2:22][CH2:21][CH2:20][O:19][C:15]2[CH:14]=[C:13]3[C:18]([C:9]([O:8][C:7]4[CH:6]=[CH:5][C:4]([NH:27][C:28]([C:30]5[C:31](=[O:43])[N:32]([C:37]6[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=6)[N:33]([CH3:36])[C:34]=5[CH3:35])=[O:29])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][CH:16]=2)[CH2:25][CH2:24]1)=[O:54])=[O:45])([CH3:50])([CH3:49])[CH3:48]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 46201942N-(3-fluoro-4-(7-(3-(1-hydroxycyclopropyl)propoxy)quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 687430721-(3-(4-(4-(2,3-dimethyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)quinolin-7-yloxy)propyl)cyclopropyl 2-(tert-but-oxycarbonylamino)acetateYield 60%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(3-fluoro-4-(7-(3-(1-hydroxycyclopropyl)propoxy)-quinolin-4-yl-oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (218 mg, 0.374 mmol), N-Boc-glycine (133.4 mg, 0.768 mmol, Alfa), and DMAP (7.03 mg, 0.058 mmol, Aladdin) in 10 mL of dichloromethane was added DCC solid (323.4 mg, 1.54 mmol, Aldrich) slowly at 0° C. The reaction was then warmed up to rt and continued to stir at rt overnight. The mixture was filtered and the solid was washed with CH2Cl2 (10 mL×2). The combined organic phases were washed with 15 mL of saturated NaHCO3 solution followed by 15 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed on a silica gel column (PE:EtOAc=1:6) to give the desired compound as a yellow solid (160 mg, 60%).

Workup

  1. filtrationThe mixture was filtered
  2. washthe solid was washed with CH2Cl2 (10 mL×2)
  3. washThe combined organic phases were washed with 15 mL of saturated NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on a silica gel column (PE:EtOAc=1:6)

Sources & evidence

ORD record
ord-a875b96794fc4de7be3226fafdf0945d
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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