Ethyl Acetate → 6-Fluoro-4-(3-phenoxyphenylamino)-1,7-naphthyridine-3-carbonitrile

HRID 2113562Notes

Reaction equation

HRID 2113562 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].[O:15]([C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CCOC(C)=O.ClC1C2C(=NC=CC=2)N=CC=1>C(OCCO)C>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][N:8]=1)[N:5]=[CH:4][C:3]([C:13]#[N:14])=[C:2]2[NH:25][C:24]1[CH:26]=[CH:27][CH:28]=[C:22]([O:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:23]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 771353-PhenoxyanilineHCID 124225244-Chloro-1,8-naphthyridineHCID 185489604-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 691845446-Fluoro-4-(3-phenoxyphenylamino)-1,7-naphthyridine-3-carbonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

In a 100 mL round-bottomed flask fitted with a condenser, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.250 g, 1.20 mmol) and 3-phenoxyaniline (0.245 g, 1.32 mmol) were taken up in 20 mL 2-ethoxyethanol and heated at reflux for 1 hour, until TLC analysis (20% EtOAc in hexanes) showed complete disappearance of the 4-chloronaphthyridine. After cooling to room temperature, the reaction mixture was partitioned between 40 mL each EtOAc and 5% Na2CO3. The aqueous layer was extracted twice more with EtOAc, and the combined organic layers washed three times with brine, dried over anhydrous MgSO4, filtered, and evaporated to give 6-fluoro-4-(3-phenoxyphenylamino)-1,7-naphthyridine-3-carbonitrile as a brown oil of sufficient purity to be used directly in the next step: 1H NMR (400 MHz, DMSO-D6) δ 6.94-7.18 (m, 6 H) 7.33-7.51 (m, 3 H) 8.15 (s, 1 H) 8.68 (s, 1 H) 9.05 (s, 1 H) 10.12 (s, 1 H).

Workup

  1. customIn a 100 mL round-bottomed flask fitted with a condenser
  2. temperatureheated
  3. customthe reaction mixture was partitioned between 40 mL each EtOAc and 5% Na2CO3
  4. extractionThe aqueous layer was extracted twice more with EtOAc
  5. washthe combined organic layers washed three times with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-408a4a744dc04dabbd5e8e316e8d8d29
Source dataset
uspto-grants-2008_10
Patent number
US07432279B2

Reaction notes

Loading…