4-Chloro-N-[4-chloro-6-(4-chlorophenylamino)-pyrimidin-5-yl]-2-fluorobenzamide → 6-chloro-8-(4-chloro-2-fluorophenyl)-9-(4-chloro-phenyl)-9H-purine

HRID 1246792Notes

Reaction equation

HRID 1246792 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([NH:8][C:9]2[C:10]([Cl:23])=[N:11][CH:12]=[N:13][C:14]=2[NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=O)=[C:4]([F:26])[CH:3]=1>O=P(Cl)(Cl)Cl.C(OCC)(=O)C>[Cl:23][C:10]1[N:11]=[CH:12][N:13]=[C:14]2[C:9]=1[N:8]=[C:6]([C:5]1[CH:24]=[CH:25][C:2]([Cl:1])=[CH:3][C:4]=1[F:26])[N:15]2[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1

Participants

4

Reactant 1

HCID 219057704-Chloro-N-[4-chloro-6-(4-chlorophenylamino)-pyrimidin-5-yl]-2-fluorobenzamide

Product 1

HCID 219058226-chloro-8-(4-chloro-2-fluorophenyl)-9-(4-chloro-phenyl)-9H-purine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

A suspension of 4-chloro-N-[4-chloro-6-(4-chlorophenylamino)-pyrimidin-5-yl]-2-fluorobenzamide I-(7A-91)a (8.3 g, 20 mmol) in POCl3 (100 ml) was heated to reflux. The light brown reaction became homogeneous over 2 hours. After refluxing 3 hours, the reaction mixture was cooled and concentrated under reduced pressure to give a viscous oil. The residue was diluted with ethyl acetate and poured over ice/aqueous sodium bicarbonate. The organic layer was separated, washed with brine, dried (Na2SO4), and concentrated. Crystallization from diethyl ether afforded product I-(7A-91)b (5.8 g, 73%) as an off-white solid: +ESI MS (M+1) 393.0; 1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 7.72 (t, J=8.1 Hz, 1H), 7.60–7.55 (m, 3H), 7.50–7.42 (m, 3H).

Workup

  1. customThe light brown reaction
  2. temperatureAfter refluxing 3 hours
  3. temperaturethe reaction mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. customto give a viscous oil
  6. additionpoured over ice/aqueous sodium bicarbonate
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customCrystallization from diethyl ether afforded product I-(7A-91)b (5.8 g, 73%) as an off-white solid

Sources & evidence

ORD record
ord-537af9816ab04559bf73467e5e6b64e8
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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