Hydrochloric Acid → HCID 75203907, compound

HRID 1482670Notes

Reaction equation

HRID 1482670 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([O:26][CH2:27][CH2:28][OH:29])=[CH:24][CH:23]=1.Cl.C(Cl)(Cl)Cl.CO>C(O)CCC>[F:20][C:5]1[C:6]([NH:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[CH:12]=[CH:13][CH:14]=2)=[N:7][C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([O:26][CH2:27][CH2:28][OH:29])=[CH:30][CH:31]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 808922-(4-Aminophenoxy)ethanolHCID 21584188Chloroform methanolHCID 86724332HCID 86724332, compound

Product 1

HCID 75203907HCID 75203907, compoundYield 18.6%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

To a solution of N-{3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]phenyl}prop-2-enamide (0.05 g) and 2-(4-aminophenoxy)ethanol (0.031 g) in 1-butanol (2 mL), was added HCl (0.3 mg). The reaction mixture was heated to reflux for 5 hr. Completion of reaction was monitored by TLC using chloroform:methanol (9:1) as mobile phase. After completion, the reaction mixture was allowed to cool at room temperature. The reaction mixture was quenched in water and neutralized with sodium bicarbonate. The mixture was extracted in ethyl acetate, organic layer washed with brine, dried over sodium sulfate and concentrated completely under reduce pressure at 50° C. The obtained semisolid was purified by preparative HPLC to give 13 mg of N-{3-[(5-fluoro-2-{[4-(2-hydroxyethoxy)phenyl]amino}pyrimidin-4-yl)amino]phenyl}prop-2-enamide. M+1=410.1 1H NMR (DMSO-d6, 400 MHz) 3.671-3.694 (t, 2H, J=4.4), 3.880-3.906 (t, 2H, J=5.2), 4.83 (br, 1H), 5.741-5.771 (dd, 1H, J=2.8, 8.4), 6.237-6.284 (dd, 1H, J=2, 15.2), 6.460-6.527 (dd, 1H, J=10, 6.8), 6.749-6.771 (d, 2H, J=8.8), 7.253-7.293 (t, 1H, J=8), 7.426-7.447 (d, 1H, J=8.4), 7.473-7.492 (d, 1H, J=7.6), 7.527-7.550 (d, 2H, J=9.2), 7.998 (s, 1H), 8.062-8.071 (d, 1H, J=3.6), 9.071 (s, 1H), 9.381 (s, 1H), 10.206 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5 hr
  3. customCompletion of reaction
  4. customThe reaction mixture was quenched in water and neutralized with sodium bicarbonate
  5. extractionThe mixture was extracted in ethyl acetate
  6. washorganic layer washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated completely
  9. customat 50° C
  10. customThe obtained semisolid was purified by preparative HPLC

Sources & evidence

ORD record
ord-d1f85033266243ab8ca46469ac2d8f09
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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