Ammonium Chloride → N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide

HRID 2203446Notes

Reaction equation

HRID 2203446 reaction equation
[CH3:1][O:2][C:3]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:4]=1[CH2:5][NH:6][C:7]1[N:12]=[CH:11][CH:10]=[CH:9][N:8]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:29][C:30]1[CH:31]=[C:32]([S:37](Cl)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:4]=1[CH2:5][N:6]([C:7]1[N:8]=[CH:9][CH:10]=[CH:11][N:12]=1)[S:37]([C:32]1[CH:33]=[CH:34][C:35]([F:36])=[C:30]([F:29])[CH:31]=1)(=[O:39])=[O:38]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27369133,4-Difluorobenzene-1-sulfonyl chlorideHCID 55026262N-[(2,4-dimethoxyphenyl)methyl]pyrimidin-2-amine

Product 1

HCID 90389104N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamideYield 73%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a cold (−78° C.) solution of N-(2,4-dimethoxybenzyl)pyrimidin-2-amine (1.85 g, 7.54 mmol) in tetrahydrofuran (20 mL) was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydrofuran, 8.3 mL, 8.3 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The mixture was cooled to −78° C. and a solution of 3,4-difluorobenzene-1-sulfonyl chloride (1.1 mL, 8.3 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. Saturated aqueous ammonium chloride (10 mL) was added, followed by with ethyl acetate (100 mL), causing a precipitate to be deposited. The solid was collected by vacuum filtration to afford N-(2,4-dimethoxybenzyl)-3,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide as a colorless solid in 73% yield (2.32 g): 1H NMR (300 MHz, CDCl3) δ8.50 (d, J=4.8 Hz, 2H), 7.74-7.60 (m, 2H), 7.16-7.06 (m, 2H), 6.94 (t, J=4.8 Hz, 1H), 6.39 (dd, J=8.3, 2.2 Hz, 1H), 6.28 (d, J=2.1 Hz, 1H), 5.41 (s, 2H), 3.76 (s, 3H), 3.45 (s, 3H); 19F NMR (282 MHz, CDCl3) δ−129.9 (d, J=20.7 Hz, 1F), −135.4 (d, J=20.7 Hz, 1F).

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. temperatureto warm to ambient temperature
  3. stirringstirred for 1 h
  4. filtrationThe solid was collected by vacuum filtration

Sources & evidence

ORD record
ord-4ce19b2f67034ae68912164fa9c36c95
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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