Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 2-(N-(4-iodobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate

HRID 923572Notes

Reaction equation

HRID 923572 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=2)=[O:11])=[C:5]([C:22]([F:25])([F:24])[F:23])[CH:4]=1.[I:26][C:27]1[CH:42]=[CH:41][C:30]([CH2:31][NH:32][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:29][CH:28]=1.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>[I:26][C:27]1[CH:28]=[CH:29][C:30]([CH2:31][N:32]([CH2:33][C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[C:17](=[O:18])[C:16]2[CH:20]=[CH:21][C:13]([NH:12][C:10](=[O:11])[CH2:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=3[C:22]([F:25])([F:23])[F:24])=[CH:14][CH:15]=2)=[CH:41][CH:42]=1

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 22473408N-(4-iodobenzyl)glycine tert-butyl esterHCID 710767434-(2-(4-Methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

Product 1

HCID 71111625tert-butyl 2-(N-(4-iodobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetateYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 8: To a stirring solution of 4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-18 (1.38 g, 3.92 mmol), tert-butyl 2-((4-iodobenzyl)amino)acetate INT-35 (1.36 g, 3.92 mmol) and TEA (0.82 ml, 5.88 mmol) in DMF (8 mL) was added HATU (1.56 g, 4.11 mmol). After stirring at room temperature for 2 h, the reaction mixture was diluted with EA (150 mL) and washed successively with NaHCO3 (100 mL) and brine (100 mL). The organics were pre-absorbed onto silica gel and then purified by chromatography (EA/isohexanes) to afford 2.05 g (75%) of tert-butyl 2-(N-(4-iodobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-36. LCMS-ESI (m/z) calculated for C30H30F3IN2O5: 682; found 627 [M−tBu+H]+, tR=2.90 min (Method 10). 1H NMR (400 MHz, DMSO) δ 10.33 (s, 1H), 7.76-7.68 (m, 2H), 7.62 (dd, J=7.0, 1.8 Hz, 2H), 7.44 (d, J=8.3 Hz, 1H), 7.37-7.30 (m, 2H), 7.27-7.13 (m, 3H), 7.12-6.97 (s, 1H), 4.59 (s, 1H), 4.50 (s, 1H), 3.92 (m, 2H), 3.85 (s,2H), 3.83 (s, 3H), 1.41 (s, 4.5H), 1.31 (s, 4.5H).

Workup

  1. customPrepared
  2. washwashed successively with NaHCO3 (100 mL) and brine (100 mL)
  3. customThe organics were pre-absorbed onto silica gel
  4. custompurified by chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-dae3ad03cb68484ea65bd5e21bd70468
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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