Triphosgene → HCID 178452689、化合物

HRID 405021ノート

反応式

HRID 405021 の反応式
C([O:3][C:4](=[O:49])[CH:5]([NH:33][C:34]([NH:36][C:37]1[NH:38][N:39]=[C:40]([C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[CH:41]=1)=[O:35])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:20][CH:19]=3)[O:15][N:14]=2)=[C:9]([F:32])[CH:8]=1)C.ClC(OC(=O)OC(Cl)(Cl)Cl)(Cl)Cl.C(OC(C(N)CC1C=CC(C2N=C(C3C=CC(NC(=O)OC(C)(C)C)=CC=3)ON=2)=C(F)C=1)=O)C.FC1C=CC(C2C=C(N)NN=2)=CC=1>ClCCl.C([O-])(O)=O.[Na+].N1C=CC=CC=1>[C:28]([O:27][C:25]([NH:24][C:21]1[CH:20]=[CH:19][C:18]([C:16]2[O:15][N:14]=[C:13]([C:10]3[CH:11]=[CH:12][C:7]([CH2:6][CH:5]([NH:33][C:34]([NH:36][C:37]4[NH:38][N:39]=[C:40]([C:42]5[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=5)[CH:41]=4)=[O:35])[C:4]([OH:49])=[O:3])=[CH:8][C:9]=3[F:32])[N:17]=2)=[CH:23][CH:22]=1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

参加物

8

反応物 4

HCID 94429TriphosgeneHCID 66630730Ethyl 2-amino-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)propanoateHCID 178470867HCID 178470867、化合物HCID 178507289HCID 178507289、化合物

生成物 1

HCID 178452689HCID 178452689、化合物収率 51%

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒2 回HCID 516892Sodium Bicarbonate溶媒2 回

実験手順

3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-{3-[5-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-ureido}-propionic acid ethyl ester. To a solution of bis(trichloromethyl)carbonate (189 mg, 0.66 mmol) in dichloromethane (12 mL) and saturated aqueous NaHCO3 (0.8 mL) was slowly added a solution of tert-butyl 4-(3-(4-(2-(ethoxycarbonyl)-2-aminoethyl)-2-fluorophenyl)-1,2,4-oxadiazol-5-yl)phenylcarbamate (300 mg, 0.66 mmol) in dichloromethane (12 mL) at 0° C. The reaction mixture was then stirred at room temperature for 1 hr. TLC showed the reaction was completed. Saturated aqueous NaHCO3 (18 mL), pyridine (0.3 mL), and 3-(4-fluorophenyl)-1H-pyrazol-5-amine (177 mg, 1 mmol) were added to the reaction mixture. The resulting mixture was then stirred overnight. TLC showed the reaction was completed. The layers were separated and the aqueous portion was extracted with dichloromethane (2×50 mL). The combined organic layers were washed sequentially with aq. HCl solution (1N, 2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give the title compound (343 mg, 51% yield) as a yellow solid.

後処理

  1. stirringThe resulting mixture was then stirred overnight
  2. customThe layers were separated
  3. extractionthe aqueous portion was extracted with dichloromethane (2×50 mL)
  4. washThe combined organic layers were washed sequentially with aq. HCl solution (1N, 2×50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-daaea2c766ce4b4fb0dbc90f8c5d65c7
出典データセット
uspto-grants-2014_06
特許番号
US08748412B2

反応ノート

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