Ammonium Hydroxide → HCID 25010232, compound

HRID 2093234Notes

Reaction equation

HRID 2093234 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11][C:10]=2[CH3:18])=[CH:5][C:4]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=1[CH2:29][N:30]1[C@@H:34]([CH3:35])[C@@H:33]([C:36]2[CH:41]=[CH:40][N:39]=[C:38]([CH3:42])[CH:37]=2)[O:32][C:31]1=[O:43].C(Cl)(=O)C(Cl)=O.[OH-].[NH4+].C([N:55](C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([NH2:55])=[O:17])=[CH:11][C:10]=2[CH3:18])=[CH:5][C:4]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:21][C:20]=1[CH2:29][N:30]1[C@@H:34]([CH3:35])[C@@H:33]([C:36]2[CH:41]=[CH:40][N:39]=[C:38]([CH3:42])[CH:37]=2)[O:32][C:31]1=[O:43]

Participants

7

Reactant 4

HCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 25010059HCID 25010059, compound

Product 1

HCID 25010232HCID 25010232, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4′-methoxy-2-methyl-2″-{[(4S,5R)-4-methyl-5-(2-methylpyridin-4-yl)-2-oxo-1,3-oxazolidin-3-yl]methyl}-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid (15 mg, 0.025 mmol) in CH2Cl2 (2 mL), was added 2M oxalyl chloride in CH2Cl2 (0.038 mL, 0.076 mmol) and 2 drops of DMF. The mixture was stirred at room temperature under N2 for 30 min. The reaction mixture was concentrated in vacuo. The residue was re-dissolved in THF (2 mL), then ammonium hydroxide (0.035 mL, 0.254 mmol) and diisopropylethylamine (0.013 mL, 0.076 mmol) were added. The resulting mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated in vacuo and the residue was purified by preparative HPLC reverse phase (C-18), eluting with MeCN/water. The fractions were collected and lyophilized to give 4′-methoxy-2-methyl-2″-{[(4S,5R)-4-methyl-5-(2-methylpyridin-4-yl)-2-oxo-1,3-oxazolidin-3-yl]methyl}-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxamide as a white powder. LCMS calc.=590.2; found=590.0 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture o atropisomers) δ 8.49 (t, J=4.3 Hz, 1 H); 7.77 (br s, 1 H); 7.72 (s, 0.5 H); 7.66 (br s, 1.5 H); 7.46-7.38 (m, 3 H); 7.33-7.29 (m, 1 H); 7.14 (dd, J=2.2, 7.7 Hz, 1 H); 7.09 (dd, J=6.2, 8.5 Hz, 1 H); 7.06 (s, 0.5 H); 7.01 (s, 0.5 H); 6.95 (d, J=4.3 Hz, 0.5 H); 6.90 (d, J=4.4 Hz, 0.5 H); 6.17 (br s, 1 H); 5.79 (br s, 1 H); 5.43 (d, J=8.1 Hz, 0.5 H); 5.20 (d, J=8.0 Hz, 0.5 H); 4.92 (d, J=15.9 Hz, 0.5 H); 4.86 (d, J=15.8 Hz, 0.5 H); 4.22 (d, J=15.8 Hz, 0.5 H); 4.00 (d, J=15.8 Hz, 0.5 H); 3.88 (s, 1.5 H); 3.87 (s, 1.5 H); 3.80-3.75 (m, 1 H); 2.57 (s, 1.5 H); 2.56 (s, 1.5 H); 2.39 (s, 1.5 H); 2.35 (s, 1.5 H); 0.58 (d, J=6.5 Hz, 1.5 H); 0.47 (d, J=6.5 Hz, 1.5 H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in THF (2 mL)
  3. stirringThe resulting mixture was stirred at room temperature for 3 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue was purified by preparative HPLC reverse phase (C-18)
  6. washeluting with MeCN/water
  7. customThe fractions were collected

Sources & evidence

ORD record
ord-c5a346096391497d828db75b14d9aaa6
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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