2-Chloro-6-fluoro-3-methoxybenzoic acid → N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-2-chloro-6-fluoro-N-(2-hydroxyethyl)-3-methoxybenzamide

HRID 577566Notes

Reaction equation

HRID 577566 reaction equation
[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]([F:13])[C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:38]([O:45][C:46]1[C:51]([CH2:52][NH:53][CH2:54][CH2:55][OH:56])=[C:50]([CH3:57])[CH:49]=[C:48]([CH3:58])[N:47]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>CN(C=O)C>[CH2:38]([O:45][C:46]1[C:51]([CH2:52][N:53]([CH2:54][CH2:55][OH:56])[C:4](=[O:6])[C:3]2[C:7]([F:13])=[CH:8][CH:9]=[C:10]([O:11][CH3:12])[C:2]=2[Cl:1])=[C:50]([CH3:57])[CH:49]=[C:48]([CH3:58])[N:47]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

5

Reactant 3

HCID 36999612-Chloro-6-fluoro-3-methoxybenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867236942-(((2-(Benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)amino)ethanol

Product 1

HCID 86723791N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-2-chloro-6-fluoro-N-(2-hydroxyethyl)-3-methoxybenzamideYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-chloro-6-fluoro-3-methoxy-benzoic acid (1.00 g, 4.89 mmol) in anhydrous DMF (30 mL) were added HATU (2.30 g, 5.85 mmol) and TEA (1.36 mL, 9.76 mmol). The reaction mixture was stirred for 5 minutes, then 2-[(2-benzyloxy-4,6-dimethyl-pyridin-3-ylmethyl)-amino]-ethanol (Cpd KK, 1.47 g, 5.12 mmol) was added as a solid in one portion. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL). The organic phase was separated, washed with brine (2×200 mL), dried over sodium sulfate, and concentrated under vacuum to give N-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-2-chloro-6-fluoro-N-(2-hydroxyethyl)-3-methoxybenzamide (124a, 2.31 g, 100%) as a gum.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 2 hours
  3. customThe reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL)
  4. customThe organic phase was separated
  5. washwashed with brine (2×200 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-31deb89ff8014444865833ab66605c94
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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