2-Chloro-4,6-difluoroaniline → HCID 59436014, compound

HRID 1802487Notes

Reaction equation

HRID 1802487 reaction equation
Cl[C:2]1[C:11]2[CH:12]=[CH:13][N:14]=[C:15]([O:16][CH2:17][CH3:18])[C:10]=2[C:9]2[C:4](=[CH:5][CH:6]=[N:7][CH:8]=2)[N:3]=1.Cl[C:20]1[C:29]2[CH:30]=[CH:31][N:32]=[C:33]([Cl:34])[C:28]=2[C:27]2[C:22](=[CH:23][CH:24]=[N:25][CH:26]=2)[N:21]=1.[Cl:35][C:36]1[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[C:37]=1[NH2:38].CC(C)([O-])C.[Na+]>C1COCC1>[Cl:35][C:36]1[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[C:37]=1[NH:38][C:2]1[C:11]2[CH:12]=[CH:13][N:14]=[C:15]([O:16][CH2:17][CH3:18])[C:10]=2[C:9]2[C:4](=[CH:5][CH:6]=[N:7][CH:8]=2)[N:3]=1.[Cl:34][C:33]1[C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[N:25][CH:26]=3)[N:21]=[C:20]([NH:38][C:37]3[C:39]([F:44])=[CH:40][C:41]([F:43])=[CH:42][C:36]=3[Cl:35])[C:29]=2[CH:30]=[CH:31][N:32]=1

Participants

7

Reactant 4

HCID 27340832-Chloro-4,6-difluoroanilineHCID 23676156Sodium t-butoxideHCID 59436091HCID 59436091, compoundHCID 59436097HCID 59436097, compound

Product 2

HCID 59436014HCID 59436014, compoundHCID 59436106HCID 59436106, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 1.5:1 mixture of 6-chloro-10-ethoxypyrido[4,3-c]-1,6-naphthyridine and 6,10-dichloropyrido[4,3-c]-1,6-naphthyridine (1.5 g) in THF (25 mL) was added 2-chloro-4,6 difluoro aniline (945 mg, 5.78 mmol) and sodium tert-butoxide (1.65 g, 17 mmol). The solution was heated to 85° C. for 40 min then cooled to room temperature and extracted with EtOAc and brine. The organic layers were dried with MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified on silica gel (100% hexanes to 100% EtOAc, gradient elution) which provided N-(2-chloro-4,6-difluorophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine and 10-chloro-N-(2-chloro-4,6-difluorophenyl)pyrido[4,3-c]-1,6-naphthyridin-6-amine.

Workup

  1. temperaturethen cooled to room temperature
  2. extractionextracted with EtOAc and brine
  3. dry with materialThe organic layers were dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified on silica gel (100% hexanes to 100% EtOAc, gradient elution) which

Sources & evidence

ORD record
ord-d4a4e8bfa27e41ac9cc1803335175697
Source dataset
uspto-grants-2013_01
Patent number
US08349865B2

Reaction notes

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