Triphosgene → HCID 178452689, 화합물

HRID 405021노트

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HRID 405021 반응식
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]

참가 물질

8

반응물 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, 화합물HCID 178507289HCID 178507289, 화합물

생성물 1

HCID 178452689HCID 178452689, 화합물수율 51%

시약·촉매·용매 3

HCID 1049Pyridine용매HCID 6344Dichloromethane용매2회HCID 516892Sodium Bicarbonate용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-daaea2c766ce4b4fb0dbc90f8c5d65c7
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748412B2

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