Sodium hydride → HCID 57818614, compound

HRID 1500036Notes

Reaction equation

HRID 1500036 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)[N:3]=1.[H-].[Na+].[S:21]([NH2:25])([NH2:24])(=[O:23])=[O:22]>CN(C=O)C>[F:8][C:7]1[C:2]([NH:24][S:21]([NH2:25])(=[O:23])=[O:22])=[N:3][C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[N:5][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 82267SulfamideHCID 57818820HCID 57818820, compound

Product 1

HCID 57818614HCID 57818614, compoundYield 7.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a magnetically stirred solution of 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine* (1.3 g, 4.84 mmol) in dry DMF (5 mL) was added a pre-mixed suspension of 60% NaH (0.45 g, 10.65 mmol) and sulfamide (0.93 g, 9.68 mmol) in dry DMF (5 mL). The resulting off-white suspension was stirred at room temperature for 72 hrs. The orange suspension was then heated to 50° C. for 48 hours and cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and brine solution. The organic extract was dried over Na2SO4, filtered, and evaporated. The crude material was purified by column chromatography on normal phase silica using a gradient of EtOAc/Hex and reverse phase using a gradient of H2O/CH3CN to yield [5-fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-yl]sulfamide (115 mg, 7.2% yield) as a white solid: mp 126-130° C.; 1H NMR (300 MHz, CD3OD) δ 8.01 (d, J=3.63 Hz, 1H), 7.25 (m, 1H), 7.01 (m, 2H), 6.88 (m, 1H), 5.37 (s, 2H), 3.78 (s, 3H); MS (ESI) m/z 326.9 (M−H)−. *The 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine intermediate was prepared as described in the synthesis of 31.

Workup

  1. temperatureThe orange suspension was then heated to 50° C. for 48 hours
  2. temperaturecooled to room temperature
  3. customThe reaction mixture was partitioned between ethyl acetate and brine solution
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified by column chromatography on normal phase silica using a gradient of EtOAc/Hex

Sources & evidence

ORD record
ord-30bcfaea17f845188cf242b67b74b693
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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