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-hydroxybenzyl)-2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido) benzamido)acetate

HRID 923561Notes

Reaction equation

HRID 923561 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([NH:12][C:13](=[O:27])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[C:23]([F:26])([F:25])[F:24])[CH:9]=[CH:8][C:4]=1[C:5](O)=[O:6].[OH:28][C:29]1[CH:44]=[CH:43][C:32]([CH2:33][NH:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:31][CH:30]=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>[OH:28][C:29]1[CH:44]=[CH:43][C:32]([CH2:33][N:34]([CH2:35][C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[C:5](=[O:6])[C:4]2[CH:8]=[CH:9][C:10]([NH:12][C:13](=[O:27])[CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[C:23]([F:26])([F:25])[F:24])=[CH:11][C:3]=2[O:2][CH3:1])=[CH:31][CH:30]=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 538343224-{[N-(boc)methylamino]methyl}phenolHCID 710767972-Methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

Product 1

HCID 71076764tert-butyl 2-(N-(4-hydroxybenzyl)-2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido) benzamido)acetateYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 6: To a stirred solution of 2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-23 (404 mg, 1.05 mmol), tert-butyl 2-((4-hydroxybenzyl)amino)acetate INT-22 (250 mg, 1.05 mmol) and TEA (367 μL, 2.63 mmol) in DMF (5 mL) was added HATU (421 mg, 1.11 mmol). After 2 h the reaction mixture was diluted with EA (100 mL) and washed with brine (2×150 mL). The organics were pre-absorbed onto silica gel and then purified by chromatography (EA/isohexanes) to afford 633 mg (99%) of tert-butyl 2-(N-(4-hydroxybenzyl)-2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-24 as a waxy solid. LCMS-ESI (m/z) calculated for C31H33F3N2O7: 602 found 601 [M−H]−, tR=2.29 min (Method 10). 1H NMR (400 MHz, DMSO 100° C.) δ 10.25 (s, 1H), 9.28 (s, 1H), 7.52-7.41 (m, 2H), 7.27-7.04 (m, 5H), 6.95 (d, J=8.0 Hz, 1H), 6.72 (dd, J=20.5, 7.9 Hz, 2H), 4.52 (br s, 1H), 4.22 (s, 1H), 3.81 (m, 9H), 3.62 (s, 1H), 1.40 (d, J=2.1 Hz, 4.5H), 1.30 (d, J=2.1 Hz, 4.5H).

Workup

  1. customPrepared
  2. washwashed with brine (2×150 mL)
  3. customThe organics were pre-absorbed onto silica gel
  4. custompurified by chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-08ac71d0459b45dd9e5b06d17d18f29c
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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