Methyl iodide → tert-Butyl 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl(methyl)carbamate

HRID 1670197Notes

Reaction equation

HRID 1670197 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:6]=1.[H-].[Na+].I[CH3:29]>CN(C=O)C.O>[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([N:11]([CH3:29])[C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH:6]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59852921Tert-butyl 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-ylcarbamate2×

Product 1

HCID 59852957tert-Butyl 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl(methyl)carbamateYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl 6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-ylcarbamate (Compound C of Example 6, 44 mg, 0.13 mmol) in anhydrous DMF (1 mL) was cooled in an ice bath and treated with 60% NaH (44 mg, 0.16 mmol) and stirred at the same temperature for 30 minutes. The reaction mixture was treated with iodomethane (10 μL, 0.15 mmol) and stirred at 0-5° C. for 10 min. The reaction mixture was allowed to warm to room temperature and stirred for 30 min. The mixture was diluted with H2O (10 mL) and extracted with EtOAc (2×10 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the product (35 mg, 74%) as a pale yellow solid. 1H NMR (DMSO-d6) δ 8.57 (d, 1H, J=1.1 Hz), 8.37 (dd, 1H, J=9.8, 3.0 Hz), 8.19 (ddd, 1H, J=9.1, 2.5, 1.0 Hz), 7.71 (dd, 1H, J=8.8, 8.8 Hz), 7.66 (s, 1H), 3.38 (s, 3H), 1.51 (s, 9H).

Workup

  1. stirringstirred at 0-5° C. for 10 min
  2. stirringstirred for 30 min
  3. extractionextracted with EtOAc (2×10 mL)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-acf1f16df6af4270a2bc062ec358775f
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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