Phthalimide potassium salt → HCID 59242117, compound

HRID 1876212Notes

Reaction equation

HRID 1876212 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH3:33])[C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=[C:13]([CH2:21][N:22]3C(=O)C4C(=CC=CC=4)C3=O)[N:12]=2)=[CH:6][C:5]=1[F:34])[CH3:2].ClCC1N=C(N(C2C=CC(OCC)=C(F)C=2)C)C2C(=CC=CC=2)N=1.C1(=O)NC(=O)C2=CC=CC=C12.[K]>CN(C=O)C.CCOC(C)=O>[NH2:22][CH2:21][C:13]1[N:12]=[C:11]([N:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][CH2:1][CH3:2])=[C:5]([F:34])[CH:6]=2)[CH3:33])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1

Participants

6

Reactant 3

HCID 24194345Phthalimide potassium saltHCID 68516772HCID 68516772, compoundHCID 68519534HCID 68519534, compound

Product 1

HCID 59242117HCID 59242117, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

2-{4-[(4-Ethoxy-3-fluoro-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione: A suspension of (2-chloromethyl-quinazolin-4-yl)-(4-ethoxy-3-fluoro-phenyl)-methyl-amine (179.1 mg, 0.52 mmol) and potassium phthalimide (104 mg, 0.56 mmol) in DMF (2 mL) was heated to 70° C. for 2 h. The reaction was cooled to rt, diluted with EtOAc, washed with 5% NaOH and H2O, dried (MgSO4), filtered and concentrated. The residue was purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%) to provide 215 mg (91%) of the title compound. 1H NMR (CDCl3) δ 7.90-7.92 (m, 2H), 7.67-7.80 (m, 3H), 7.50-7.57 (m, 3H), 6.83-7.05 (m, 4H), 6.75-6.81 (m, 1H), 5.14 (s, 2H), 4.11 (q, 2H), 3.24 (s, 3H), 1.47 (t, 3H); LC-MS (ESI+; 457 ([M+H]+)).

Workup

  1. temperatureThe reaction was cooled to rt
  2. washwashed with 5% NaOH and H2O
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%)

Sources & evidence

ORD record
ord-dfa8b394c98744969ca4f21c7b7ab19f
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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