Triethylamine → HCID 90077617, compound

HRID 2203255Notes

Reaction equation

HRID 2203255 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([OH:14])=O)=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=1.C(N(CC)CC)C.[CH3:33][O:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH2:40])=[CH:37][CH:36]=1>S(Cl)(Cl)=O.O1CCCC1>[CH3:33][O:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH:40][C:12]([C:6]2[CH:7]=[N:8][C:9]3[C:4]([C:5]=2[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=2)=[N:3][C:2]([Cl:1])=[CH:11][CH:10]=3)=[O:14])=[CH:37][CH:36]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 754524-MethoxybenzylamineHCID 90077540HCID 90077540, compound

Product 1

HCID 90077617HCID 90077617, compoundYield 94.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
75 °C

Procedure

6-chloro-4-(3-(trifluoromethyl)phenylamino)-1,5-naphthyridine-3-carboxylic acid (3.6 g, 9.8 mmol) was suspended in 50 mL sulfinyl chloride. The resulting mixture was heated under stirring to 75° C. and reacted for 4 hrs while keeping at the same temperature. The reaction was naturally cooled to room temperature, and concentrated to obtain a yellow solid. The resulting solid was dispersed in 100 mL tetrahydrofuran. To the resulting mixture was added dropwise a mixture of triethylamine (3.03 g, 30 mmol) and para-methoxybenzylamine (1.6 g, 13 mmol) at 0° C. The reaction mixture was stirred at room temperature for 4 hrs, and rotary-evaporated to remove the solvent. To the residue was added 300 mL water. The resulting mixture was filtered by suction. The filter cake was washed with ethyl acetate and petroleum ether (volume ratio 1/10, 100 mL) and dried to obtain a pale yellow solid of N-(4-methoxybenzyl)-6-chloro-4-(3-(trifluoromethyl)phenylamino)-1,5-naphthyridine-3-carboxamide (4.5 g).

Workup

  1. temperatureThe resulting mixture was heated
  2. customreacted for 4 hrs
  3. temperatureThe reaction was naturally cooled to room temperature
  4. concentrationconcentrated
  5. customto obtain a yellow solid
  6. additionTo the resulting mixture was added dropwise
  7. stirringThe reaction mixture was stirred at room temperature for 4 hrs
  8. customrotary-evaporated
  9. customto remove the solvent
  10. additionTo the residue was added 300 mL water
  11. filtrationThe resulting mixture was filtered by suction
  12. washThe filter cake was washed with ethyl acetate and petroleum ether (volume ratio 1/10, 100 mL)
  13. customdried

Sources & evidence

ORD record
ord-f169755b1344473cb1ceb9e62d5fe50f
Source dataset
uspto-grants-2016_06
Patent number
US09365572B2

Reaction notes

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