Triethylamine → 3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-[(6-p-tolyl-pyridine-2-carbonyl)-amino]-propionic acid

HRID 405019Notes

Reaction equation

HRID 405019 reaction equation
C([O:3][C:4](=[O:49])[CH:5]([NH:33][C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]2[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=2)[N:37]=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.C1(C)C=CC(C2N=C(C(O)=O)C=CC=2)=CC=1.C(OC(=O)C(N)CC1C=CC(C2N=C(C3C=CC(NC(OC(C)(C)C)=O)=CC=3)ON=2)=C(F)C=1)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.C([O-])(O)=O.[Na+]>ClCCl>[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]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]5[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][CH:43]=5)[N:37]=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])([CH3:30])[CH3:29]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 127849986-(4-Methylphenyl)pyridine-2-carboxylic acidHCID 66630730Ethyl 2-amino-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)propanoateHCID 666313083-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}-2-[(6-p-tolyl-pyridine-2-carbonyl)-amino]-propionic acid ethyl ester

Product 1

HCID 533718963-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-[(6-p-tolyl-pyridine-2-carbonyl)-amino]-propionic acidYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}-2-[(6-p-tolyl-pyridine-2-carbonyl)-amino]-propionic acid ethyl ester. A mixture of 6-p-tolyl-pyridine-2-carboxylic acid (47 mg, 0.1 mmol), 2-amino-3-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}propionic acid ethyl ester (30 mg), HATU (46 mg, 0.12 mmol), and Et3N (15 mg, 0.15 mmol) in dichloromethane (5 mL) was stirred at room temperature overnight. TLC showed the reaction was completed. Saturated aqueous NaHCO3 (20 mL) was added to the mixture, and organic and aqueous layers were separated. The aqueous portion was extracted with dichloromethane (2×50 mL). The combined organic layers were washed sequentially with aq. HCl (1N, 2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated to give the title compound (53 mg, 80% yield).

Workup

  1. customorganic and aqueous layers were separated
  2. extractionThe aqueous portion was extracted with dichloromethane (2×50 mL)
  3. washThe combined organic layers were washed sequentially with aq. HCl (1N, 2×50 mL) and brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was evaporated

Sources & evidence

ORD record
ord-24e28333b32043bcb2ec2a8d72d94ada
Source dataset
uspto-grants-2014_06
Patent number
US08748412B2

Reaction notes

Loading…