Sodium Iodide → 5-Benzyl-3-methyl-6-propyl-5H-isoxazolo[5,4-d]pyrimidin-4-one

HRID 1794592Notes

Reaction equation

HRID 1794592 reaction equation
[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][C:7]([CH2:12][CH2:13][CH3:14])=[N:6][C:5]=2[O:4][N:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Na+].[I-]>C1COCC1>[CH2:25]([N:8]1[C:9](=[O:11])[C:10]2[C:2]([CH3:1])=[N:3][O:4][C:5]=2[N:6]=[C:7]1[CH2:12][CH2:13][CH3:14])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7498Benzyl BromideHCID 2733832Lithium HexamethyldisilazideHCID 1359795693-methyl-6-propyl-5H-isoxazolo[5,4-d]pyrimidin-4-one

Product 1

HCID 222222815-Benzyl-3-methyl-6-propyl-5H-isoxazolo[5,4-d]pyrimidin-4-oneYield 20.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of the compound of Example 1 Step 2 (1.8 g, 9.3 mmol) in anhydrous THF (40 mL) at room temperature was treated with 1M lithium hexamethyldisilazide (13.9 mL, 13.9 mmol) and stirred for 1 h. The mixture was then treated with benzylbromide (2.37 g, 1.65 mL, 13.9 mmol) and NaI (0.15 g, 1.0 mmol). The mixture was stirred at 50° C. for 40 h, then cooled to room temperature. The mixture was partitioned between ether and brine and the organic phase was washed with water. The organic phase was concentrated under vacuum and purified by flash chromatography on SiO2 (15% EtOAc/Hexane) to afford the desired product as a white solid (540 mg, 20%); 1H NMR (DMSO-d6) δ 7.35 (m, 5H), 5.41 (s, 2H), 2.79 (t, J=7.5 Hz, 2H), 2.53 (s, 3H), 1.72 (q, J=7.5 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H); LC/MS (ESI): 284 (M+H)+.

Workup

  1. stirringThe mixture was stirred at 50° C. for 40 h
  2. customThe mixture was partitioned between ether and brine
  3. washthe organic phase was washed with water
  4. concentrationThe organic phase was concentrated under vacuum
  5. custompurified by flash chromatography on SiO2 (15% EtOAc/Hexane)

Sources & evidence

ORD record
ord-e928a16e775a45678529cce43f19dad0
Source dataset
uspto-grants-2006_04
Patent number
US07022850B2

Reaction notes

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