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 1517869노트

반응식

HRID 1517869 반응식
[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]

참가 물질

6

반응물 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

생성물 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)acetate수율 60%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-a875b96794fc4de7be3226fafdf0945d
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232294B2

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