Triethylamine → 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-methoxy-N,N,2-trimethyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxamide

HRID 607115Notes

Reaction equation

HRID 607115 reaction equation
[F:1][C:2]([F:50])([F:49])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:38]4[CH:43]=CC(C(O)=O)=[CH:40][C:39]=4[CH3:47])[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.CNC.Cl.[CH3:56][N:57]([CH3:66])[CH2:58][CH2:59][CH2:60]N=C=NCC.O.N1([OH:77])C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.CCOC(C)=O>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:38]4[CH:43]=[CH:60][C:59]([C:58]([N:57]([CH3:56])[CH3:66])=[O:77])=[CH:40][C:39]=4[CH3:47])[CH:33]=[CH:34][C:35]=3[O:36][CH3:37])[C@H:14]2[CH3:48])[CH:4]=[C:3]([C:2]([F:1])([F:50])[F:49])[CH:8]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 250105732''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Product 1

HCID 250091602''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-methoxy-N,N,2-trimethyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2″-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid (EXAMPLE 30,300 mg, 0.42 mmol), N-methylmethanamine hydrochloride (41 mg, 0.50 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (121 mg, 0.63 mmol), 1H-1,2,3-benzotriazol-1-ol hydrate (86 mg, 0.56 mmol) and triethylamine (146 μL, 1.05 mmol) were stirred in DCM (5 mL) at room temperature for 1.5 hours. LCMS of aliquot at this time indicated formation of the desired product and complete consumption of starting material. Crude mixture was diluted with MeCN and purified by reversed phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with (acetonitrile+0.1% v/v TFA)/(water+0.1% v/v TFA) (10% to 100% organic in 10 min, hold 100% for 2 min, 20 mL/min) to give a solid foam. This solid foam was dissolved in EtOAc and washed with NaHCO3 (sat., aq) and then with water. Aqueous layers were separated from the extracts. The combined aqueous phases were back extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered and then concentrated in vacuo to afford the title compound. LCMS (ESI) calc.=738.21; found=739.41 (M+1)+. 1H NMR (CDCl3, 500 MHz, 1:1 mixture of atropisomers): δ 7.85 (s, 0.5H), 7.71 (s, 0.5H), 7.69 (s, 1H), 7.67-7.62 (m, 2.5H), 7.44 (d, J=8 Hz, 0.5H), 7.41 (d, J=8.5 Hz, 0.5H), 7.36 (t, J=7.5 Hz, 1H), 7.32 (d, J=8 Hz, 1H), 7.25 (s, 0.5H), 7.23 (s, 1H), 7.19 (d, J=8 Hz, 0.5H), 7.12 (t, J=2 Hz, 1H), 7.07 (d, J=7 Hz, 0.5H), 7.05 (d, J=7 Hz, 0.5H), 5.58 (d, J=8 Hz, 0.5H), 5.30 (d, J=8 Hz, 0.5H), 4.96 (d, J=16 Hz, 1H), 4.16 (d, J=16 Hz, 0.5H), 3.97 (d, J=15.5 Hz, 0.5H), 3.86 (s, 3H), 3.81-3.73 (m, 1H), 3.11 (s, 3H), 3.02 (s, 3H), 2.33 (s, 1.5H), 2.27 (s, 1.5H), 0.54 (d, J=6.5 Hz, 1.5H), 0.41 (d, J=6.5 Hz, 1.5H).

Workup

  1. customformation of the desired product and complete consumption of starting material
  2. additionCrude mixture was diluted with MeCN
  3. custompurified by reversed phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  4. washeluting with (acetonitrile+0.1% v/v TFA)/(water+0.1% v/v TFA) (10% to 100% organic in 10 min, hold 100% for 2 min, 20 mL/min)
  5. customto give a solid foam
  6. washwashed with NaHCO3 (sat., aq)
  7. customAqueous layers were separated from the extracts
  8. extractionThe combined aqueous phases were back extracted with EtOAc
  9. dry with materialThe combined extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0e0bcc2c845f4aa094d26f0ee0909f9a
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

Loading…