Sodium hydride → HCID 87056011, compound

HRID 1428920Notes

Reaction equation

HRID 1428920 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:22][C:23]([N:25]([CH3:36])[C:26]1[CH:35]=[CH:34][C:29]2[N:30]=[C:31]([CH3:33])[O:32][C:28]=2[CH:27]=1)=[O:24]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[N:10]([CH2:22][C:23]([N:25]([CH3:36])[C:26]3[CH:35]=[CH:34][C:29]4[N:30]=[C:31]([CH3:33])[O:32][C:28]=4[CH:27]=3)=[O:24])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67160967HCID 67160967, compoundHCID 90418141Acetamide, 2-bromo-N-methyl-N-(2-methyl-6-benzoxazolyl)-

Product 1

HCID 87056011HCID 87056011, compoundYield 24.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-(3-chlorophenyl)phthalazin-1(2H)-one (0.5 g, 1.94 mmol) in DMF (20 mL) was added NaH (60%) (0.116 g, 2.91 mmol) portionwise at 0° C. After stirring for 30 min, 2-bromo-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl) acetamide (0.55 g, 1.94 mmol) in DMF (2 mL) was added dropwise and the reaction mixture warmed to rt overnight. The reaction was quenched with water and the solid collected by filtration. The crude was purified by column chromatography (60-70% EtOAc/hexane) to give 2-(4-(3-chlorophenyl)-1-oxophthalazin-2(1H)-yl-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl)acetamide (0.22 g), (MS: ESI +ve, 459.17 [M+H]). 1H NMR: (400 MHz, DMSO) δ: 2.63 (s, 3H), 3.24 (s, 3H), 4.73 (s, 2H), 7.44-7.46 (d, J=8.0, 1H), 7.55-7.66 (m, 4H), 7.69-7.74 (q, 2H), 7.93 (s, 3H), 8.29-8.31 (d, J=7.2, 1H). Representative compounds of the invention were prepared in a similar manner to examples 1 from 4-chlorophthalazin-1(2H)-one, the corresponding boronic acid or ester, and the appropriate alkylating agent (scheme 1).

Workup

  1. customThe reaction was quenched with water
  2. filtrationthe solid collected by filtration
  3. customThe crude was purified by column chromatography (60-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-820751ef0c974ad69e8abc2aecd0bf6b
Source dataset
uspto-grants-2015_01
Patent number
US08937178B2

Reaction notes

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