Sodium hydride → HCID 10116483, compound

HRID 2416638Notes

Reaction equation

HRID 2416638 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]3[CH:13]=[CH:14][C:15]([C:17]4[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=4)=[CH:16][C:9]=23)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[S:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[C:31](Cl)=[O:32]>CN(C=O)C.C1COCC1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][N:11]=[C:10]3[CH:13]=[CH:14][C:15]([C:17]4[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:31]([C:27]5[S:26][CH:30]=[CH:29][CH:28]=5)=[O:32])[N:18]=4)=[CH:16][C:9]=23)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 789282-Thiophenecarbonyl chlorideHCID 22632292HCID 22632292, compound

Product 1

HCID 10116483HCID 10116483, compoundYield 24.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

4-[3-(3-bromophenyl)-benzo[c]isoxazol-5-yl]-pyrimidin-2-ylamine (100 mg; 0.272 mmol) was dissolved in 3 mL of a mixture (2:1) of dry DMF/THF and stirred under a nitrogen atmosphere at ambient temperature. Sodium hydride (15 mg, 0.375 mmol, 60% oil dispersion) was added To the reaction and stirred for 30 minutes. Thiophenecarbonylchloride (32 μL; 43.7 mg; 0.299 mmol) in 500 μL of dry DMF was added dropwise over 2 minutes and the reaction was stirred for 18 hours at ambient temperature. Workup was affected by removing the solvents under reduced pressure and the resulting residue was triturated with methyltertbutyl ether. The crude solid was purified via silica column chromatography with 5% ethanol in methylenechloride to yield 32 mg of a tan powder; 24% yield. 1H NMR (500 MHz, DMSO-d6) δ 11.2 (s, 1H), 8.92 (s, 1H), 8.88 (d, 1H), 8.39 (d, 1H), 8.35 (s, 1H), 8.3 (d, 1H), 8.23 (d, 1H), 8.15 (d, 1H), 7.95 (d, 1H), 7.9 (d, 1H), 7.87 (d, 1H), 7.65 (t, 1H), 7.24 (t, 1H) in ppm. LC-MS (ES+) m/e=477/479 (M+H).

Workup

  1. stirringstirred for 30 minutes
  2. stirringthe reaction was stirred for 18 hours at ambient temperature
  3. customby removing the solvents under reduced pressure
  4. customthe resulting residue was triturated with methyltertbutyl ether
  5. customThe crude solid was purified via silica column chromatography with 5% ethanol in methylenechloride

Sources & evidence

ORD record
ord-e2aa31306b93462eb4d042bc994fd6c7
Source dataset
uspto-grants-2004_11
Patent number
US06825190B2

Reaction notes

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