Potassium Carbonate → HCID 21991801, compound

HRID 2102455Notes

Reaction equation

HRID 2102455 reaction equation
FC(F)(F)C(O)=O.[Cl:8]C1C=C([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](O)=[C:24](OC)[CH:25]=3)[N:20]=[CH:19][N:18]=2)C=CC=1Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C>[ClH:8].[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17]([NH2:16])=[N:18][CH:19]=1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 136335147HCID 136335147, compound

Product 1

HCID 21991801HCID 21991801, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol trifluoroacetate (salt) (0.150 g, 0.322 mmol), (3-endo)-3-[(methylsulfonyl)oxy]-8-azabicyclo[3.2.1]octane (0.106 g, 0.483 mmol), and potassium carbonate (0.220 g, 1.60 mmol) in N,N-dimethylacetamide (1.1 mL) was heated in a sealed tube at 100° C. for 12 h, followed by 48 h at room temperature. The crude reaction mixture was filtered through celite using methanol eluent, and the solvents were removed in vacuo. The residue was purified by HPLC (reverse-phase, acetonitrile/water/0.1% TFA). Upon removal of solvent, the product was taken up in methanol and treated with Bio-Rad AG 1-X8 resin (hydroxide form) until pH 8. The product was filtered and concentrated in vacuo, then taken up in methanol and treated with 4.0 M hydrogen chloride in dioxane (0.050 mL). Removal of solvent in vacuo provided 48.7 mg (31%) of N-(3,4-dichlorophenyl)-7-{[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}-6-methyloxy)quinazolin-4-amine hydrochloride. 1H NMR (400 MHz, d6-DMSO): 10.69 (s, 1H), 8.92 (s, 1H), 8.32 (s, 1H), 8.17 (d, 1H), 7.81 (m, 2H), 7.75 (d, 1H), 5.05 (m, 1H), 4.02 (s, 3H), 2.69 (d, 2H), 2.39 (m, 1H), 2.29-2.18 (m, 6H); MS (EI) for C23H24N4O2Cl2: 459 (MH+).

Workup

  1. customThe crude reaction mixture
  2. filtrationwas filtered through celite
  3. customthe solvents were removed in vacuo
  4. customThe residue was purified by HPLC (reverse-phase, acetonitrile/water/0.1% TFA)
  5. customUpon removal of solvent
  6. additiontreated with Bio-Rad AG
  7. filtrationThe product was filtered
  8. concentrationconcentrated in vacuo
  9. additiontreated with 4.0 M hydrogen chloride in dioxane (0.050 mL)
  10. customRemoval of solvent in vacuo

Sources & evidence

ORD record
ord-99af7d5efa314405b30ea4beabfb7329
Source dataset
uspto-grants-2009_08
Patent number
US07576074B2

Reaction notes

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