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

HRID 1517865Notes

Reaction equation

HRID 1517865 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:26][C:27]([C:29]2[C:30](=[O:42])[N:31]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:32]([CH3:35])[C:33]=2[CH3:34])=[O:28])[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][C:22]3([OH:25])[CH2:24][CH2:23]3)=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[C:43]([NH:50][CH2:51][C:52](O)=[O:53])([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl>[C:46]([O:45][C:43]([NH:50][CH2:51][C:52]([O:25][C:22]1([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:26][C:27]([C:29]5[C:30](=[O:42])[N:31]([C:36]6[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=6)[N:32]([CH3:35])[C:33]=5[CH3:34])=[O:28])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][CH:16]=2)[CH2:23][CH2:24]1)=[O:53])=[O:44])([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 59278563HCID 59278563, compound

Product 1

HCID 666938911-(2-(4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)quinolin-7-yloxy)ethyl)cyclopropyl 2-(tert-butoxy-carbonylamino)acetateYield 70%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(3-fluoro-4-(7-(2-(1-hydroxycyclopropyl)ethoxy)quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (218 mg, 0.384 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 reaction mixture was filtered and the solid was washed with dichloromethane (10 mL×2). The combined organic phases were washed with 20 mL of saturated NaNCO3 solution followed by 20 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed on a silica gel column (PE: EA=1:6) to give the desired compound as a yellow solid (190 mg, 70%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe solid was washed with dichloromethane (10 mL×2)
  3. washThe combined organic phases were washed with 20 mL of saturated NaNCO3 solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on a silica gel column (PE: EA=1:6)

Sources & evidence

ORD record
ord-4c68338b4f5f4ba2a284cd90c70710da
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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