Acetic Acid → HCID 18753460, compound

HRID 547203Notes

Reaction equation

HRID 547203 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21](OC)OC)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:28])[CH:3]=1.C(O)(C(F)(F)F)=O.[CH:36]1([NH2:41])[CH2:40][CH2:39][CH2:38][CH2:37]1.C(O)(=O)C.C([BH3-])#N.[Na+]>O>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][NH:41][CH:36]4[CH2:40][CH2:39][CH2:38][CH2:37]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:28])[CH:3]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 2906CyclopentylamineHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 22478201HCID 22478201, compound

Product 1

HCID 18753460HCID 18753460, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-(2,2-dimethoxyethoxy)-6-methoxyquinazoline (210 mg, 0.52 mmol), water (5 ml) and TFA (5 ml) was stirred at ambient temperature for 3 hours then heated at 60° C. for 1 hour. The solution was allowed to cool, then diluted with water and the resulting precipitate was collected by filtration and dried. The solid was dissolved in methanol (10 ml) and cyclopentylamine (0.057 ml, 0.57 mmol) and dried 3 Å molecular sieves (2.5g) were added. The mixture was stirred for 30 minutes, glacial acetic acid (0.20 ml, 3.2 mmol) and sodium cyanoborohydride (150 mg, 2.4 mmol) were added and the reaction stirred for 4 hours then left to stand for 18 homs. The insolubles were removed by filtration and the solvent was removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (1008/1). The purified product was triturated with ether/hexane, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-7-(2-cyclopentylaminoethoxy)-6-methoxyquinazoline (80 mg, 36%).

Workup

  1. temperaturethen heated at 60° C. for 1 hour
  2. temperatureto cool
  3. filtrationthe resulting precipitate was collected by filtration
  4. customdried
  5. dissolutionThe solid was dissolved in methanol (10 ml)
  6. additionwere added
  7. stirringThe mixture was stirred for 30 minutes
  8. stirringthe reaction stirred for 4 hours
  9. waitthen left
  10. customThe insolubles were removed by filtration
  11. customthe solvent was removed from the filtrate by evaporation
  12. customThe residue was purified by column chromatography
  13. washeluting with methylene chloride/methanol/aqueous ammonia (1008/1)
  14. customThe purified product was triturated with ether/hexane
  15. filtrationcollected by filtration
  16. customdried

Sources & evidence

ORD record
ord-a282a1cf0ad1410ca1c1463ff583e1fe
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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