Trifluoroacetic acid → HCID 58960247, compound

HRID 2068102Notes

Reaction equation

HRID 2068102 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][CH2:25][CH2:26][N:27]5[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][N:8]=2)[CH:3]=[CH:2]1.FC(F)(F)C(O)=O>ClCCl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][CH2:25][CH2:26][N:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][N:8]=2)[CH:3]=[CH:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 670192314-(7-Azaindol-5-yloxy)-7-{3-[4-(tert-butoxycarbonyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline

Product 1

HCID 58960247HCID 58960247, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(7-Azaindol-5-yloxy)-7-{3-[4-(tert-butoxycarbonyl)piperazin-1-yl]propoxy}-6-methoxyquinazoline (1.9 g, 3.55 mmol) was suspended in dichloromethane (60 ml) and trifluoroacetic acid (2 ml) added dropwise. All solid dissolved at this point giving an orange solution which was stirred for 3 hours at ambient temperature. More trifluoroacetic acid (4 ml) was added and the mixture stirred overnight. The mixture was concentrated under reduced pressure and the residue concentrated from dichloromethane (×3) and toluene to remove trifluoroacetic acid. The residue was dissolved in methanol, placed on an Isolute SCX column, washed with methanol and then eluted with 7N ammonia in methanol. The product was then purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (95/5 followed by 93/7) to give 4-(7-azaindol-5-yloxy)-6-methoxy-7-(3-piperazin-1-ylpropoxy)quinazoline (660 mg, 43%) as a white foam.

Workup

  1. dissolutionAll solid dissolved at this point
  2. customgiving an orange solution which
  3. stirringthe mixture stirred overnight
  4. concentrationThe mixture was concentrated under reduced pressure
  5. concentrationthe residue concentrated from dichloromethane (×3) and toluene
  6. customto remove trifluoroacetic acid
  7. dissolutionThe residue was dissolved in methanol
  8. washwashed with methanol
  9. washeluted with 7N ammonia in methanol
  10. customThe product was then purified by column chromatography
  11. washeluting with methylene chloride/methanol (saturated with ammonia) (95/5 followed by 93/7)

Sources & evidence

ORD record
ord-88b6f0fba98c42e5a06cfaf3e962368d
Source dataset
uspto-grants-2012_10
Patent number
US08293902B2

Reaction notes

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