Trifluoroacetic acid → (R)-2-(-3-amino-piperidin-1-yl)-3-(but-2-ynyl)-5-(4-methyl-quinazolin-2-ylmethyl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

HRID 1446048Notes

Reaction equation

HRID 1446048 reaction equation
[CH2:1]([N:5]1[C:9]2[C:10](=[O:26])[N:11]([CH2:14][C:15]3[N:24]=[C:23]([CH3:25])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[N:12]=[CH:13][C:8]=2[N:7]=[C:6]1[N:27]1[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33]C(=O)OC(C)(C)C)[CH2:28]1)[C:2]#[C:3][CH3:4].FC(F)(F)C(O)=O>ClCCl>[NH2:33][C@@H:29]1[CH2:30][CH2:31][CH2:32][N:27]([C:6]2[N:5]([CH2:1][C:2]#[C:3][CH3:4])[C:9]3[C:10](=[O:26])[N:11]([CH2:14][C:15]4[N:24]=[C:23]([CH3:25])[C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]=4)[N:12]=[CH:13][C:8]=3[N:7]=2)[CH2:28]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58699918HCID 58699918, compound

Product 1

HCID 10003476(R)-2-(-3-amino-piperidin-1-yl)-3-(but-2-ynyl)-5-(4-methyl-quinazolin-2-ylmethyl)-3,5-dihydro-imidazo[4,5-d]pyridazin-4-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 17.2 g (31.7 mmol) tert-butyl (R)-{1-[1-(but-2-ynyl)-6-(4-methyl-quinazolin-2-ylmethyl)-7-oxo-6,7-dihydro-1H-imidazo[4,5-d]pyridazin-2-yl]-piperidin-3-yl}-carbamate in 400 ml dichloromethane was combined with 85 ml trifluoroacetic acid and stirred for three hours at ambient temperature. The mixture was evaporated to dryness at 30° C., the residue was dissolved in dichloromethane and the solution was made basic with ice-cooled saturated sodium carbonate solution. The organic phase was separated off and the aqueous phase was extracted twice more with dichloromethane. The combined organic phases were dried over sodium sulphate and the solvent was removed. The residue was purified by chromatography on silica gel (dichloromethane/methanol/ammonium hydroxide 95:5:0.1).

Workup

  1. customThe mixture was evaporated to dryness at 30° C.
  2. dissolutionthe residue was dissolved in dichloromethane
  3. temperaturecooled saturated sodium carbonate solution
  4. customThe organic phase was separated off
  5. extractionthe aqueous phase was extracted twice more with dichloromethane
  6. dry with materialThe combined organic phases were dried over sodium sulphate
  7. customthe solvent was removed
  8. customThe residue was purified by chromatography on silica gel (dichloromethane/methanol/ammonium hydroxide 95:5:0.1)

Sources & evidence

ORD record
ord-cd9cba7aaf814662957cd848337495d1
Source dataset
uspto-grants-2010_02
Patent number
US07667035B2

Reaction notes

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