2-Amino-5-(trifluoromethyl)pyridine → 7-(3-Chloropyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridin-4-amine

HRID 1724875Notes

Reaction equation

HRID 1724875 reaction equation
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][N:13]=1)=[N:7]2.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1>CCOC(C)=O>[Cl:18][C:17]1[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:27])[F:29])=[CH:22][N:21]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 575611615-Chloro-2-(3-chloropyridin-2-yl)-[1,8]naphthyridine

Product 1

HCID 575611057-(3-Chloropyridin-2-yl)-N-(5-(trifluoromethyl)pyridin-2-yl)-[1,8]naphthyridin-4-amine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of 5-chloro-2-(3-chloropyridin-2-yl)-[1,8]naphthyridine (82.5 mg, 0.3 mmol) and 2-amino-5-trifluoromethylpyridine (97.2 mg, 0.6 mmol) at 180° C. for 2.0 hours. Cool the mixture, dilute with EtOAc/1.0 N aq. NaOH (5.0 mL each), and separate the organic layer, extract the aq. layer with EtOAc (2×5 mL) and dry the combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by column chromatography using EtOAc to 2% MeOH/EtOAc as eluents to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.2 (s, 1H), 9.07 (d, 1H, J=1.9 Hz), 8.93 (d, 1H, J=1.2 Hz), 8.68 (m, 2H), 8.47 (s, 1H), 8.08 (m, 2H), 7.96 (d, 1H, J=2.2 Hz), 7.56 (dd, 1H), 7.46 (d, 1H, J=2.2 Hz). MS=402.22 (M+H).

Workup

  1. temperatureHeat
  2. temperatureCool the mixture
  3. customseparate the organic layer
  4. extractionextract the aq. layer with EtOAc (2×5 mL)
  5. dry with materialdry the combined organic layers with MgSO4
  6. filtrationFilter the dried
  7. extractionextract
  8. concentrationconcentrate under vacuum
  9. customto afford crude product
  10. customPurify by column chromatography

Sources & evidence

ORD record
ord-3d8205c88aab4099adece8d1240493f2
Source dataset
uspto-grants-2009_02
Patent number
US07488740B2

Reaction notes

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