m-Toluidine → HCID 69320816, compound

HRID 2113567Notes

Reaction equation

HRID 2113567 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9](F)[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[CH:17]=1.[NH2:23][CH2:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1>COCCOC>[CH3:22][C:18]1[CH:17]=[C:16]([NH:15][C:2]2[C:11]3[C:6](=[CH:7][N:8]=[C:9]([NH:23][CH2:24][C:25]4[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=4)[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:13]#[N:14])[CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7934m-ToluidineHCID 310183-PyridinemethanamineHCID 185489604-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile

Product 1

HCID 69320816HCID 69320816, compoundYield 2.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

In a microwave vial, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.200 g, 0.963 mmol) and m-toluidine (0.11 mL, 0.11 g, 1.1 mmol) were taken up in 5 mL DME. The vial was crimp-sealed and heated in a microwave reactor at 140° C. for 10 minutes. 3-(aminomethyl)pyridine (2.0 mL, 2.1 g, 19 mmol) was then added, and the reaction was heated at 200° C. for 30 minutes. To work up the reaction, the vial contents were partitioned between EtOAc and brine. The aqueous layer was extracted with additional EtOAc, and the combined organic extracts washed with water and evaporated. The crude product was purified twice by preparative HPLC, and lyophilized to give a fluffy, bright yellow solid (7.5 mg, 2.1% yield): 1H NMR (400 MHz, DMSO-D6) δ 2.31 (s, 3 H) 4.55 (d, J=4.0 Hz, 2 H) 7.06 (s, 3 H) 7.16 (s, 1 H) 7.21-7.39 (m, 2 H) 7.44 (s, 1 H) 7.75 (d, J=7.6 Hz, 1 H) 8.22 (s, 1 H) 8.43 (s, 1 H) 8.59 (s, 1 H) 8.82 (s, 1 H) 9.61 (br s, 1 H).

Workup

  1. customThe vial was crimp-sealed
  2. temperaturethe reaction was heated at 200° C. for 30 minutes
  3. customthe reaction
  4. customthe vial contents were partitioned between EtOAc and brine
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. washthe combined organic extracts washed with water
  7. customevaporated
  8. customThe crude product was purified twice by preparative HPLC

Sources & evidence

ORD record
ord-569387c4d73a46c0bfbf59b0e380a578
Source dataset
uspto-grants-2008_10
Patent number
US07432279B2

Reaction notes

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