Phthalimide potassium salt → HCID 59242016, compound

HRID 1876215Notes

Reaction equation

HRID 1876215 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)=[C:6]([F:34])[CH:5]=1)[CH3:2].ClCC1N=C(N(C2C=CC(OCC)=CC=2F)C)C2C(=CC=CC=2)N=1.C1(=O)NC(=O)C2=CC=CC=C12.[K]>CN(C)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])=[CH:5][C:6]=2[F:34])[CH3:33])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1

Participants

5

Reactant 3

HCID 24194345Phthalimide potassium saltHCID 685145582-{4-[(4-Ethoxy-2-fluoro-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dioneHCID 68516792(2-Chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-methyl-amine

Product 1

HCID 59242016HCID 59242016, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2-{4-[(4-Ethoxy-2-fluoro-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-isoindole-1,3-dione: To (2-chloromethyl-quinazolin-4-yl)-(4-ethoxy-2-fluoro-phenyl)-methyl-amine (341 mg 0.94 mmol) in N,N-dimethylformamide (3 mL) was added potassium phthalimide (381 mg, 2.1 mmol). The reaction was heated to 70° C. for 2.5 hours. The reaction was quenched with H2O and diluted with EtOAc. The aqueous phase was extracted with EtOAc (3×10 mL). The combined organic phases were washed with brine, dried (MgSO4), concentrated and purified by gradient MPLC (0-100%, EtOAc/Hexane, SiO2) to give 380 mg (90%) of the title compound as a solid. 1H NMR (MeOH-d4) δ 7.95-7.93 (dd, 2H), 7.86-7.84 (dd, 2H), 7.68-7.62 (m, 2H), 7.23-7.18 (t, 1H), 7.11-7.05 (m, 2, H), 6.77 (d, 2H), 5.04 (s, 2H), 4.03 (q, 2H), 3.20 (s, 3H), 1.39 (t, 3H); LC-MS (ESI+; 457 ([M+H]+)).

Workup

  1. customThe reaction was quenched with H2O
  2. additiondiluted with EtOAc
  3. extractionThe aqueous phase was extracted with EtOAc (3×10 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. custompurified by gradient MPLC (0-100%, EtOAc/Hexane, SiO2)

Sources & evidence

ORD record
ord-eace364a12ae411b9ee6d43a7621089d
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

Loading…