Triphosgene → HCID 178452689, compound

HRID 405021Notes

Reaction equation

HRID 405021 reaction equation
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]

Participants

8

Reactant 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, compoundHCID 178507289HCID 178507289, compound

Product 1

HCID 178452689HCID 178452689, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-daaea2c766ce4b4fb0dbc90f8c5d65c7
Source dataset
uspto-grants-2014_06
Patent number
US08748412B2

Reaction notes

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