Phosphorus oxychloride → HCID 57476867, compound

HRID 857953Notes

Reaction equation

HRID 857953 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[NH:11][CH:10]=[N:9][C:8]2=O)(=[O:3])[CH3:2].C(N(CC)C(C)C)(C)C.P(Cl)(Cl)(Cl)=O.[Cl:32][C:33]1[C:34]([F:40])=[C:35]([CH:37]=[CH:38][CH:39]=1)[NH2:36]>C1(C)C=CC=CC=1>[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[CH:10][N:9]=[C:8]2[NH:36][C:35]1[CH:37]=[CH:38][CH:39]=[C:33]([Cl:32])[C:34]=1[F:40])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychloride2×HCID 750143-Chloro-2-fluoroanilineHCID 81531DiisopropylethylamineHCID 178486913HCID 178486913, compound

Product 1

HCID 57476867HCID 57476867, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

6-Acetoxy-7-methoxy-4(1H)-quinazolinone (150 g; prepared as described in WO96/15118, Example 39 thereof), N,N-diisopropylethylamine (123 ml) and toluene (1275 ml) were stirred at 70° C., under nitrogen. Phosphorus oxychloride (150 ml) was added over 15 minutes to the slurry at 70° C. The mixture was held at 70° C. for 2 hours to complete the chlorination. A dark brown solution formed after 30 minutes following addition of the phosphorus oxychloride. Toluene (680 ml) was added to the reaction mixture, followed by addition of 3-chloro-2-fluoroaniline (78 ml) over 10 minutes at 70° C. On completion of the addition, a solid precipitated resulting in a beige slurry. The slurry was held at 70° C. for 1 hour and then cooled to ambient temperature. The reaction mixture was filtered and washed with toluene (2×300 ml), aqueous IMS (2×450 ml and IMS (2×450 ml). The solid was left to pull dry on the filter overnight to give 6-acetoxy-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline.HCl salt; NMR Spectrum: (DMSO d6) 2.39 (s, 3H); 4.02 (s, 3H); 7.36 (t, 1H); 7.58 (s, 1H); 7.64 (t, 1H); 8.79 (s, 1H) 8.91 (s, 1H); 11.93 (bs 1H); Mass Spectrum: M+H362.

Workup

  1. customprepared
  2. customA dark brown solution formed after 30 minutes
  3. additionOn completion of the addition
  4. customa solid precipitated
  5. customresulting in a beige slurry
  6. waitThe slurry was held at 70° C. for 1 hour
  7. filtrationThe reaction mixture was filtered
  8. washwashed with toluene (2×300 ml), aqueous IMS (2×450 ml and IMS (2×450 ml)
  9. waitThe solid was left
  10. customto pull dry on the filter overnight

Sources & evidence

ORD record
ord-2be1eda31af9494ca36556613f3f3cca
Source dataset
uspto-grants-2006_12
Patent number
US07148230B2

Reaction notes

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