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

HRID 545067Notes

Reaction equation

HRID 545067 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[N:17]=[CH:16][C:15]([NH2:18])=[CH:14][C:13]=1[C:19]([F:22])([F:21])[F:20])=[N:7]2.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=1>CCOC(C)=O>[NH2:18][C:15]1[CH:14]=[C:13]([C:19]([F:22])([F:21])[F:20])[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:23][C:24]4[CH:29]=[CH:28][C:27]([C:30]([F:32])([F:31])[F:33])=[CH:26][N:25]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:17][CH:16]=1

Participants

4

Reactant 2

HCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 586456816-(5-Chloro-1,8-naphthyridin-2-yl)-5-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 586455757-(5-Amino-3-(trifluoromethyl)pyridin-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 6-(5-chloro-1,8-naphthyridin-2-yl)-5-(trifluoromethyl)pyridin-3-amine (64.8 mg, 0.2 mmol) and 2-amino-5-trifluoromethylpyridine (64 mg, 0.4 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 aqueous layer with EtOAc (3×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify the crude product by HPLC to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.15 (s, 1H), 8.96 (d, 1H, J=2.2 Hz), 8.89 (m, 1H), 8.67 (s, 1H), 8.41 (m, 1H), 8.29(s, 1H), 8.25 (d, 1H, J=0.7 Hz), 8.07 (dd, 1H), 7.94 (d, 1H, J=2.2 Hz), 7.41 (d, 1H, J=0.6 Hz), 6.17 (s, 2H). MS=451.36 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. temperatureHeat
  2. temperatureCool the mixture
  3. customseparate the organic layer
  4. extractionExtract the aqueous layer with EtOAc (3×5 mL)
  5. customdry
  6. filtrationFilter the dried
  7. extractionextract
  8. concentrationconcentrate under vacuum
  9. customto afford crude product
  10. customPurify the crude product by HPLC

Sources & evidence

ORD record
ord-8da1527f7122497abef64252c1be4520
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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