Sodium hydride → HCID 67013703, compound

HRID 1433107Notes

Reaction equation

HRID 1433107 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][CH2:10][N:11]2[CH2:16][CH2:15][NH:14][C:13](=[O:17])[C:12]2=[O:18])=[CH:4][CH:3]=1.[H-].[Na+].[NH2:21][C:22]1[C:31]2[C:26](=[CH:27][C:28]([CH2:32]Cl)=[CH:29][CH:30]=2)[N:25]=[CH:24][N:23]=1>CN(C=O)C>[NH2:21][C:22]1[C:31]2[C:26](=[CH:27][C:28]([CH2:32][N:14]3[CH2:15][CH2:16][N:11]([CH2:10][CH:9]=[CH:8][C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[C:12](=[O:18])[C:13]3=[O:17])=[CH:29][CH:30]=2)[N:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 272813087-(Chloromethyl)quinazolin-4-amineHCID 68898467HCID 68898467, compound

Product 1

HCID 67013703HCID 67013703, compoundYield 43.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 1-[3-(4-chloro-phenyl)-allyl]-piperazine-2,3-dione (60 mg, 0.23 mmol) in 1.5 mL of DMF is added NaH (10 mg of a 60% dispersion in mineral oil, 0.24 mmol). The mixture is heated at 55° C. for 20 min. To the solution is added 4-amino-7-chloromethyl-quinazoline (49 mg, 0.25 mmol), and the resulting mixture is heated at 55° C. for 20 min as a white precipitate is formed. After this time, reaction mixture is quenched with a few drops of H2O and MeOH, then concentrated. The crude product is purified by RP-HPLC, eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) over 30 minutes, and the appropriate product fractions are combined and lyopholized to provide the title compound (56 mg, 0.10 mmol) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ 9.78 (bs, 2H), 8.83 (s, 1H), 8.40 (s, 1H), 7.72 (d, 1H), 7.65 (s, 1H), 7.49 (d, 2H), 7.38 (d, 2H), 6.61 (d, 1H), 6.30 (dt, 1H), 4.80 (s, 2H), 4.18 (d, 2H), 3.59 (m, 4H). ISP MS, [M+H]+=422.

Workup

  1. temperaturethe resulting mixture is heated at 55° C. for 20 min as a white precipitate
  2. customis formed
  3. customAfter this time, reaction mixture
  4. customis quenched with a few drops of H2O and MeOH
  5. concentrationconcentrated
  6. customThe crude product is purified by RP-HPLC
  7. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) over 30 minutes

Sources & evidence

ORD record
ord-7fadfb5133274159a8406cf1a74e0c10
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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