Lithium Hexamethyldisilazide → HCID 86298931, compound

HRID 1428928Notes

Reaction equation

HRID 1428928 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=3)[C:11](=[O:20])[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:32][C:33]([N:35]([CH3:46])[C:36]1[CH:45]=[CH:44][C:39]2[N:40]=[C:41]([CH3:43])[O:42][C:38]=2[CH:37]=1)=[O:34]>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=3)[C:11](=[O:20])[N:10]([CH2:32][C:33]([N:35]([CH3:46])[C:36]3[CH:45]=[CH:44][C:39]4[N:40]=[C:41]([CH3:43])[O:42][C:38]=4[CH:37]=3)=[O:34])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 90418141Acetamide, 2-bromo-N-methyl-N-(2-methyl-6-benzoxazolyl)-HCID 90418704HCID 90418704, compound

Product 1

HCID 86298931HCID 86298931, compoundYield 74.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 0° C. solution of 4-(3-fluorophenyl)-7-methoxyphthalazin-1(2H)-one (7.0 g, 25.9 mmol) in THF (160 mL) was treated with LiHMDS (1M in THF) (38 mL, 38 mmol) and stirred for 30 min. 2-Bromo-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl)acetamide (7.33 g, 25.9 mmol) in THF (40 mL) was added dropwise and stirring was maintained at rt for 16 h. The reaction mixture was diluted with water (200 mL) and the product extracted with EtOAc (3×150 mL). The organics were washed with brine (100 mL), dried over Na2SO4, and concentrated. The crude was triturated with MeOH (250 mL) to yield 2-(4-(3-fluorophenyl)-7-methoxy-1-oxophthalazin-2(1H)-yl)-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl)acetamide (9.1 g, 74%). (472.87 [M+H]) 1H NMR: (400 MHz, DMSO) δ: 2.62 (s, 3H), 3.33 (s, 3H), 4.95 (s, 3H), 4.73 (s, 2H), 7.37-7.43 (m, 4H), 7.48-7.51 (d, J=2.4, 8.8, 1H), 7.58-7.73 (m, 4H), 7.90 (s, 1H).

Workup

  1. stirringstirring
  2. extractionthe product extracted with EtOAc (3×150 mL)
  3. washThe organics were washed with brine (100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude was triturated with MeOH (250 mL)

Sources & evidence

ORD record
ord-b3b7106aed294b88b4ee192ffead3bd8
Source dataset
uspto-grants-2015_01
Patent number
US08937178B2

Reaction notes

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