Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (S)-tert-Butyl 2-(5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)-2-oxopyridin-1(2H)-yl)acetate

HRID 2370853Notes

Reaction equation

HRID 2370853 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH2:15])[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11].[C:23]([O:27][C:28](=[O:40])[CH2:29][N:30]1[C:35](=[O:36])[CH:34]=[CH:33][C:32]([C:37](O)=[O:38])=[CH:31]1)([CH3:26])([CH3:25])[CH3:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[F:2][C:3]1[CH:4]=[C:5]([C@H:14]([NH:15][C:37]([C:32]2[CH:33]=[CH:34][C:35](=[O:36])[N:30]([CH2:29][C:28]([O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:40])[CH:31]=2)=[O:38])[C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11]

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 711653941-(2-(tert-Butoxy)-2-oxoethyl)-6-oxo-1,6-dihydropyridine-3-carboxylic AcidHCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2×

Product 1

HCID 71165370(S)-tert-Butyl 2-(5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)-2-oxopyridin-1(2H)-yl)acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

A solution of (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (400 mg, 1.174 mmol, Intermediate 6), 1-(2-(tert-butoxy)-2-oxoethyl)-6-oxo-1,6-dihydropyridine-3-carboxylic acid (327 mg, 1.292 mmol) and HATU (491 mg, 1.292 mmol) in DMF (10 mL) was treated with TEA (0.490 mL, 3.52 mmol). The reaction was then stirred at 23° C. under nitrogen. After 17 h, the solution was diluted with EtOAc (100 mL) and washed with brine (100 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluent: 5-30% EtOAc/DCM), affording the title compound as a colorless oil. The compound was taken forward to the next step. MS (ESI, positive ion) m/z: 540.2 (M+H).

Workup

  1. washwashed with brine (100 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. custompurified by silica gel chromatography (eluent: 5-30% EtOAc/DCM)

Sources & evidence

ORD record
ord-3b50ed05e4094b259bbc91ccd1a59bb2
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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