Trifluoroacetic acid → HCID 59519003, compound

HRID 1161873Notes

Reaction equation

HRID 1161873 reaction equation
C(OC([N:8]1[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][N:11]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[C:29]([O:34][CH3:35])[CH:28]=2)[N:21]([CH2:36][C:37](=[O:42])[NH:38][CH:39]([CH3:41])[CH3:40])[C:20]3=[O:43])[CH2:10][CH:9]1[CH3:44])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C:22]2[N:21]([CH2:36][C:37]([NH:38][CH:39]([CH3:41])[CH3:40])=[O:42])[C:20](=[O:43])[C:19]3[C:24](=[CH:25][CH:26]=[C:17]([N:11]4[CH2:12][C:13]([CH3:16])([CH3:15])[CH2:14][NH:8][CH:9]([CH3:44])[CH2:10]4)[CH:18]=3)[N:23]=2)=[CH:28][C:29]=1[O:34][CH3:35]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59519081HCID 59519081, compound3×

Product 1

HCID 59519003HCID 59519003, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

4-[2-(4-Fluoro-3-methoxyphenyl)-3-(isopropylcarbamoylmethyl)-4-oxo-3,4-dihydroquinazolin-6-yl]-2,6,6-trimethylperhydro-1,4-diazepine-1-carboxylic acid tert-butyl ester (120 mg, 0.197 mmol) was dissolved in DCM (6 mL) and TFA (3 mL) added. The reaction was stirred at room temperature for 4 h. Product mixture was poured directly onto an SCX cartridge and product eluted with 2N NH3/MeOH. Solvent was evaporated under reduced pressure to afford a red solid. Product was diluted with MeOH (20 mL) and heated at reflux temperature with activated carbon. The mixture was filtered through a celite pad, solvent evaporated under reduced pressure and the resultant product recrystallised from ethanol:heptane. This afforded 2-[2-(4-fluoro-3-methoxyphenyl)-4-oxo-6-(3,6,6-trimethylperhydro-1,4-diazepin-1-yl)-4H-quinazolin-3-yl]-N-isopropylacetamide (EXAMPLE 8a) (74 mg, 0.145 mmol, 74%). Data for 2-[2-(4-fluoro-3-methoxyphenyl)-4-oxo-6-(3,6,6-trimethylperhydro-1,4-diazepin-1-yl)-4H-quinazolin-3-yl]-N-isopropylacetamide (EXAMPLE 8a): MS (ESI) m/z: 510 ([M+H]+).

Workup

  1. additionProduct mixture was poured directly onto an SCX cartridge and product
  2. washeluted with 2N NH3/MeOH
  3. customSolvent was evaporated under reduced pressure
  4. customto afford a red solid
  5. temperatureheated
  6. temperatureat reflux temperature with activated carbon
  7. filtrationThe mixture was filtered through a celite pad, solvent
  8. customevaporated under reduced pressure
  9. customthe resultant product recrystallised from ethanol

Sources & evidence

ORD record
ord-85f3e419afc54a639e16693ad2619d57
Source dataset
uspto-grants-2010_10
Patent number
US07820649B2

Reaction notes

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