Water → N-(3-Chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-4-quinazolinamine

HRID 563867Notes

Reaction equation

HRID 563867 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16](S(C4C=CC=CC=4)(=O)=O)=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[OH:32][C@H:33]1[CH2:37][CH2:36][O:35][CH2:34]1.C1COCC1.O>C(O)(C)(C)C.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:32][C@H:33]4[CH2:37][CH2:36][O:35][CH2:34]4)=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 24742986(7-Phenylsulfonyl-6-nitro-chinazolin-4-yl)-(3-chlor-4-fluor-phenyl)-amin

Product 1

HCID 54376755N-(3-Chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-4-quinazolinamine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
25 °C

Procedure

810 g of 4-(3-chloro-4-fluoro-phenylamino)-7-(phenylsulphonyl)-6-nitro-quinazoline and 175.5 g (S)-3-hydroxytetrahydrofuran (1.3 eq) are placed at 20° C. in 1.04 l tert-butanol and 198 ml DMF, 2556 g K-tert.-butoxide in THF (24%) (3.6 eq) are added dropwise at 20° C. and then stirred for 4 h at 25° C. After a further 2 h at 40° C. the mixture is heated to 45° C. for about 2 h. 2.8 l of water are added and then about 3 l solvent are distilled off under reduced pressure. 2.8 l water are added again and about 900 ml solvent are distilled off under reduced pressure. After the addition of 1.6 l methanol the mixture is cooled to 20° C. The suspension is suction filtered and rinsed with a mixture of 3.2 l water and 1.6 l methanol. The residue is dried overnight at 50° C. under reduced pressure.

Workup

  1. temperatureAfter a further 2 h at 40° C. the mixture is heated to 45° C. for about 2 h
  2. distillationabout 3 l solvent are distilled off under reduced pressure
  3. addition2.8 l water are added again
  4. distillationabout 900 ml solvent are distilled off under reduced pressure
  5. additionAfter the addition of 1.6 l methanol the mixture
  6. temperatureis cooled to 20° C
  7. filtrationsuction filtered
  8. washrinsed with a mixture of 3.2 l water and 1.6 l methanol
  9. customThe residue is dried overnight at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-5cf921d6c346431fa8d8038eccb72c22
Source dataset
uspto-grants-2011_11
Patent number
US08067593B2

Reaction notes

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