Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → methyl 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate

HRID 923623Notes

Reaction equation

HRID 923623 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:31]=[CH:30][C:22]([CH2:23][NH:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])=[CH:21][CH:20]=4)[N:15]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[F:32][C:33]1[CH:41]=[C:40]([NH:42][C:43](=[O:57])[CH2:44][C:45]2[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][C:46]=2[C:53]([F:56])([F:55])[F:54])[CH:39]=[CH:38][C:34]=1[C:35](O)=[O:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[F:32][C:33]1[CH:41]=[C:40]([NH:42][C:43](=[O:57])[CH2:44][C:45]2[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][C:46]=2[C:53]([F:55])([F:56])[F:54])[CH:39]=[CH:38][C:34]=1[C:35]([N:24]([CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH2:23][C:22]1[CH:30]=[CH:31][C:19]([C:16]2[N:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=4)=[CH:13][CH:12]=3)[O:18][N:17]=2)=[CH:20][CH:21]=1)=[O:36]

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 710768612-Fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acidHCID 71112506Methyl 2-((4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)amino)acetate

Product 1

HCID 71112503methyl 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetateYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 6. To a suspension of methyl 2-((4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)amino)acetate INT-77 (50 mg, 0.121 mmol) and 2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-78 (44.9 mg, 0.121 mmol) in DMF (2 mL) were added HATU (50.6 mg, 0.133 mmol) and TEA (42.1 μL, 0.302 mmol). The reaction mixture was stirred at room temperature. After 60 h the reaction mixture was diluted with EA (20 mL) and washed with NaHCO3 (2×20 mL) and 1 M HCl (2×20 mL). The organics were dried over MgSO4 and concentrated in vacuo to afford 91 mg (98%) of methyl 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-79 as a pale yellow solid. LCMS-ESI (m/z) calculated for C42H34F4N4O6: 766; found 767 [M+H]+, tR=3.27 min (Method 10).

Workup

  1. customPrepared
  2. washwashed with NaHCO3 (2×20 mL) and 1 M HCl (2×20 mL)
  3. dry with materialThe organics were dried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f185fe0833a34a449faf54a1150b87b3
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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