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

HRID 1517877Notes

Reaction equation

HRID 1517877 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:25][C:26]([C:28]2[C:29](=[O:41])[N:30]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[N:31]([CH3:34])[C:32]=2[CH3:33])=[O:27])[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][C:21]3([OH:24])[CH2:23][CH2:22]3)=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.[C:42]([NH:49][CH2:50][C:51](O)=[O:52])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl>[C:45]([O:44][C:42]([NH:49][CH2:50][C:51]([O:24][C:21]1([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:25][C:26]([C:28]5[C:29](=[O:41])[N:30]([C:35]6[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=6)[N:31]([CH3:34])[C:32]=5[CH3:33])=[O:27])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][CH:16]=2)[CH2:22][CH2:23]1)=[O:52])=[O:43])([CH3:48])([CH3:47])[CH3:46]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 66670625N-(3-fluoro-4-(7-((1-hydroxycyclopropyl)methoxy)quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 666938521-((4-(4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamido)-2-fluorophenoxy)quinolin-7-yloxy)methyl)cyclopropyl 2-(tert-butoxycarbonylamino)acetateYield 78.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(3-fluoro-4-(7-((1-hydroxycyclopropyl)methoxy)-quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (100 mg, 0.18 mmol), N-Boc-glycine (63 mg, 0.36 mmol, Alfa), and DMAP (3 mg, 0.018 mmol, Aladdin) in 10 mL of dichloromethane was added DCC (189 mg, 0.9 mmol, Aldrich) slowly at 0° C. After stirring at rt overnight, the mixture was filtered and washed with dichloromethane (10 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed on a silica gel column (PE: EtOAc=1:6) to give the title compound as a yellow solid (100 mg, 78%).

Workup

  1. filtrationthe mixture was filtered
  2. washwashed with dichloromethane (10 mL×2)
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed on a silica gel column (PE: EtOAc=1:6)

Sources & evidence

ORD record
ord-f7160e3d0833426ab5fa9f3cbae3c9db
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

Loading…