Triethylamine → 2-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amine

HRID 606088Notes

Reaction equation

HRID 606088 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](Cl)=[N:9][OH:10])=[CH:4][CH:3]=1.[Cl:12][C:13]1[C:18]([N+:19]([O-:21])=[O:20])=[C:17]([NH:22][CH2:23][C:24]#[CH:25])[C:16]([CH3:26])=[C:15]([CH3:27])[N:14]=1.C(N(CC)CC)C>ClCCl>[Cl:12][C:13]1[C:18]([N+:19]([O-:21])=[O:20])=[C:17]([NH:22][CH2:23][C:24]2[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH:25]=2)[C:16]([CH3:26])=[C:15]([CH3:27])[N:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27563164-fluoro-N-hydroxybenzenecarboximidoyl chlorideHCID 862476282-chloro-5,6-dimethyl-3-nitro-N-prop-2-ynylpyridin-4-amine

Product 1

HCID 866168882-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amineYield 76.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

Under a nitrogen atmosphere, 4-fluoro-N-hydroxybenzenecarboximidoyl chloride (52.0 g, 225 mmol), prepared as described in Parts A through C of Example 11, was added to a solution of 2-chloro-5,6-dimethyl-3-nitro-N-prop-2-ynylpyridin-4-amine (26.92 g, 112.3 mmol) in anhydrous dichloromethane (1 L) at room temperature. Triethylamine (25 g, 250 mmol) was added; a precipitate formed. The resulting mixture was heated at 40° C. under nitrogen for 16 hours, diluted with dichloromethane, washed sequentially with aqueous potassium carbonate, water, and brine; dried over sodium sulfate; filtered; and concentrated under reduced pressure to a suspension. The suspension was filtered to isolate a yellow solid, which was washed with diethyl ether and dried under vacuum to provide 32.45 g of 2-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amine.

Workup

  1. customa precipitate formed
  2. washwashed sequentially with aqueous potassium carbonate, water, and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationand concentrated under reduced pressure to a suspension
  6. filtrationThe suspension was filtered
  7. customto isolate a yellow solid, which
  8. washwas washed with diethyl ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-c73055667db649d89f8bf3b3c68b9982
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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