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 1517869ノート

反応式

HRID 1517869 の反応式
[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]

参加物

6

反応物 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

生成物 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)acetate収率 60%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-a875b96794fc4de7be3226fafdf0945d
出典データセット
uspto-grants-2012_07
特許番号
US08232294B2

反応ノート

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