HCID 89872718, compound → HCID 72195030, compound

HRID 515393Notes

Reaction equation

HRID 515393 reaction equation
[CH:1]1([C:5]2[O:9][C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]4[CH:22]=[CH:21][C:20]([CH:23]5[CH2:28][O:27][CH:26]([CH2:29][C:30]([O:32]CC6C=CC=CC=6)=[O:31])[CH2:25][CH2:24]5)=[CH:19][CH:18]=4)=[CH:13][CH:12]=3)=[N:7][N:6]=2)[CH2:4][CH2:3][CH2:2]1>CCOC(C)=O.[OH-].[OH-].[Pd+2]>[CH:1]1([C:5]2[O:9][C:8]([NH:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]4[CH:22]=[CH:21][C:20]([CH:23]5[CH2:28][O:27][CH:26]([CH2:29][C:30]([OH:32])=[O:31])[CH2:25][CH2:24]5)=[CH:19][CH:18]=4)=[CH:15][CH:16]=3)=[N:7][N:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 1

HCID 89872718HCID 89872718, compound

Product 1

HCID 72195030HCID 72195030, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 9942167Palladium hydroxideSolvent

Procedure

Benzyl 2-(5-(4′-((5-cyclobutyl-1,3,4-oxadiazol-2-yl)amino)-[1,1′-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate was dissolved in EtOAc and hydrogenated with 10% Pd(OH)2/C under H2 balloon for 1 hr. The reaction mixture was filtered off to remove the catalyst and the filtrate was concentrated. The residue was purified by reverse HPLC (10 to 50% ACN-water (0.1% NH4OH) with X-bridge C8 column) to give the title compound 19.8 mg. HR/MS [M+H]+: found 434.2060, calc. 434.2080. RT: 2.61 (Condition L). The ratio of cis to trans was determined to be ˜1.1:1 by NMR studies. cis-isomer: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.47 (m, 1H), 1.51-1.62 (m, 1H), 1.86-2.13 (m, 4H), 2.27-2.46 (m, 6H), 2.83 (t, J=3.79 Hz, 1H), 3.62-3.79 (m, 2H), 3.81-3.94 (m, 1H), 4.02 (dd, J=11.62, 3.28 Hz, 1H), 7.48 (d, J=8.34 Hz, 2H), 7.53-7.68 (m, 6H), 10.50 (br. s., 1H). trans-isomer 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31-1.47 (m, 1H), 1.73-2.13 (m, 5H), 2.24-2.46 (m, 6H), 2.75 (ddd, J=11.37, 7.45, 4.17 Hz, 1H), 3.35-3.44 (m, 1H), 3.62-3.79 (m, 2H), 3.81-3.94 (m, 1H), 7.32 (d, J=8.34 Hz, 2H), 7.53-7.68 (m, 6H), 10.50 (br. s., 1H).

Workup

  1. filtrationThe reaction mixture was filtered off
  2. customto remove the catalyst
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by reverse HPLC (10 to 50% ACN-water (0.1% NH4OH) with X-bridge C8 column)

Sources & evidence

ORD record
ord-920b7e731fe644d8b90088c09b06e57e
Source dataset
uspto-grants-2015_08
Patent number
US09108956B2

Reaction notes

Loading…