Potassium Iodide → 3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-(2-piperidin-1-yl-pyrimidin-4-ylamino)-propionic acid

HRID 405022Notes

Reaction equation

HRID 405022 reaction equation
C([O:3][C:4](=[O:41])[CH:5]([NH:33][C:34]1[CH:39]=[CH:38][N:37]=[C:36](Cl)[N:35]=1)[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.C(OC(=O)C(N)CC1C=CC(C2N=C([C:59]3[CH:64]=[CH:63][C:62]([NH:65][C:66](OC(C)(C)C)=O)=CC=3)ON=2)=C(F)C=1)C.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].ClC1N=C(Cl)C=CN=1>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[Br-]>[C:28]([O:27][C:25]([NH:24][C:21]1[CH:22]=[CH:23][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]4[CH:39]=[CH:38][N:37]=[C:36]([N:65]5[CH2:62][CH2:63][CH2:64][CH2:59][CH2:66]5)[N:35]=4)[C:4]([OH:3])=[O:41])=[CH:8][C:9]=3[F:32])[N:17]=2)=[CH:19][CH:20]=1)=[O:26])([CH3:29])([CH3:31])[CH3:30]

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 66630730Ethyl 2-amino-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)propanoateHCID 866607833-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-(2-chloro-pyrimidin-4-ylamino)-propionic acid ethyl ester

Product 1

HCID 666317953-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-(2-piperidin-1-yl-pyrimidin-4-ylamino)-propionic acid

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-(2-chloro-pyrimidin-4-ylamino)-propionic acid ethyl ester. To solution of 2-Amino-3-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}propionic acid ethyl ester in DMF (20 mL) were added sodium carbonate (360 mg, 3.4 mmol), potassium iodide (10 mg), TBAB (10 mg), and 2,4-dichloro-pyrimidine (503 mg, 3.4 mmol). The mixture was heated at 50° C. for 4 hrs. The mixture was cooled to room temperature and partitioned between ethyl acetate and water. The combined organic layers were washed with brine, dried over sodium sulfate, filtrated, concentrated, and purified by chromatography to give the title compound (96 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltrated
  6. concentrationconcentrated
  7. custompurified by chromatography

Sources & evidence

ORD record
ord-b67db9a80ed34386a8f6c04ab3671bbc
Source dataset
uspto-grants-2014_06
Patent number
US08748412B2

Reaction notes

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