Hydrazine hydrate (1:1) → HCID 59242131, compound

HRID 1876196Notes

Reaction equation

HRID 1876196 reaction equation
Cl[CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.C1(=O)[NH:28]C(=O)C2=CC=CC=C12.[K].O.NN>CN(C=O)C.CCOC(C)=O>[NH2:28][CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH3:23])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1

Participants

6

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 24194345Phthalimide potassium saltHCID 68517238HCID 68517238, compound

Product 1

HCID 59242131HCID 59242131, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture (2-chloromethyl-quinazolin-4-yl)-(4-ethoxy-phenyl)-methyl-amine (73 mg, 0.22 mmol) and potassium phthalimide (57 mg, 0.31 mmol) in DMF (1 mL) was heated at 70° C. for 2 h. The reaction was diluted with EtOAc and washed with H2O. The aqueous phase was extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine, filtered through Na2SO4 and concentrated. The intermediate was dissolved in EtOH (5 mL), treated with hydrazine monohydrate (81 mg, 1.62 mmol) and stirred overnight. The reaction mixture was quenched with H2O and diluted with EtOAc. The aqueous and organic phases were separated and the aqueous phase extracted with EtOAc (2×10 mL). The combined organic phases were washed with brine, filtered over Na2SO4 and concentrated. Purification by gradient MPLC (SiO2, MeOH/CH2Cl2 w/0.1% NH4OH, 0-20%) provided 21 mg (31%) of the title compound. 1H NMR (CDCl3) δ 7.75 (d, 1H), 7.53 (ddd, 1H), 7.10 (d, 2H), 7.0 (m, 2H), 6.9 (d, 2H), 4.06 (s, 2H), 4.04 (q, 2H), 3.6 (s, 3H), 2.07 (s(br), 2H), 1.45 (t, 3H); LC-MS (ESI+; 309 ([M+H]+)).

Workup

  1. washwashed with H2O
  2. extractionThe aqueous phase was extracted with EtOAc (2×10 mL)
  3. washThe combined organic phases were washed with brine
  4. filtrationfiltered through Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe intermediate was dissolved in EtOH (5 mL)
  7. customThe reaction mixture was quenched with H2O
  8. additiondiluted with EtOAc
  9. customThe aqueous and organic phases were separated
  10. extractionthe aqueous phase extracted with EtOAc (2×10 mL)
  11. washThe combined organic phases were washed with brine
  12. filtrationfiltered over Na2SO4
  13. concentrationconcentrated
  14. customPurification by gradient MPLC (SiO2, MeOH/CH2Cl2 w/0.1% NH4OH, 0-20%)

Sources & evidence

ORD record
ord-7f94e52282654da5a98eb3332e057c0b
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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