Aniline → HCID 71621158, compound

HRID 2174241Notes

Reaction equation

HRID 2174241 reaction equation
[CH2:1]([NH:3][C:4](=[O:24])[NH:5][C:6]1[CH:16]=[C:15]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:9]([C:10]([O:12]CC)=O)=[CH:8][N:7]=1)[CH3:2].[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C[Al](C)C>C1COCC1>[CH2:1]([NH:3][C:4](=[O:24])[NH:5][C:6]1[CH:16]=[C:15]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:9]([C:10]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:12])=[CH:8][N:7]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6115AnilineHCID 16682925TrimethylaluminumHCID 89650076HCID 89650076, compound

Product 1

HCID 71621158HCID 71621158, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
125 °C

Procedure

A solution of ethyl 6-(3-ethylureido)-4-(pyridin-3-ylamino)nicotinate (0.60 g, 1.82 mmol) and aniline (250 μL, 2.73 mmol) in THF (10 mL) was purged with nitrogen for 15 minutes. To this solution was added trimethylaluminium (2M in toluene, 5.40 mL, 10.80 mmol) dropwise over 10-15 min. The reaction mixture was heated at 125° C. for 30 min in a microwave reactor. The reaction mass was then quenched with water and extracted with EtOAc (3×1000 mL). The organics were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC to afford Compound 13 (0.28 g, 41%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 10.32 (s, 1H), 9.89 (s, 1H), 9.15 (s, 1H), 8.59 (s, 1H), 8.54 (s, 1H), 8.35 (d, J=4.8 Hz, 1H), 7.93 (br s, 1H), 7.73 (t, J=8.0 Hz, 3H), 7.45-7.41 (m, 1H), 7.37 (t, J=7.6 Hz, 2H), 7.23 (s, 1H), 7.13 (t, J=7.6 Hz, 1H), 3.16-3.13 (m, 2H), 1.08 (t, J=7.2 Hz, 3H). [M+H]+ m/z=377.22.

Workup

  1. customThe reaction mass was then quenched with water
  2. extractionextracted with EtOAc (3×1000 mL)
  3. washwashed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-bc7ae2d118b34363b214909d8e6f7a7a
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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