Formaldehyde → 4-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 2203461Notes

Reaction equation

HRID 2203461 reaction equation
N[C:2]1[C:6]2[CH:7]=[C:8]([C:11]3[CH:45]=[C:44]([Cl:46])[CH:43]=[CH:42][C:12]=3[O:13][C:14]3[C:19]([F:20])=[CH:18][C:17]([S:21]([N:24]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:32]=4[O:39][CH3:40])[C:25]4[S:29][N:28]=[CH:27][N:26]=4)(=[O:23])=[O:22])=[C:16]([F:41])[CH:15]=3)[CH:9]=[CH:10][C:5]=2[O:4][N:3]=1.[CH2:47]=O.[C:49]([BH3-])#[N:50].[Na+]>C(O)(=O)C.C(OCC)(=O)C.[OH-].[Na+]>[Cl:46][C:44]1[CH:43]=[CH:42][C:12]([O:13][C:14]2[C:19]([F:20])=[CH:18][C:17]([S:21]([N:24]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:32]=3[O:39][CH3:40])[C:25]3[S:29][N:28]=[CH:27][N:26]=3)(=[O:22])=[O:23])=[C:16]([F:41])[CH:15]=2)=[C:11]([C:8]2[CH:9]=[CH:10][C:5]3[O:4][N:3]=[C:2]([N:50]([CH3:49])[CH3:47])[C:6]=3[CH:7]=2)[CH:45]=1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 903892074-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Product 1

HCID 895553634-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideYield 35%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a mixture of 4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.686 g, 1.0 mmol) and paraformaldehyde (0.30 g, 10.0 mmol) in acetic acid (3 mL) was added sodium cyanoborohydride (0.19 g, 3.0 mmol) and the reaction mixture was stirred at ambient temperature for 16 h. The mixture was diluted with ethyl acetate (100 mL) and 1 M aqueous sodium hydroxide (10 mL) was added. The organic phase was washed with 1 M aqueous sodium hydroxide (10 mL) and brine (10 mL), dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 25-100% gradient of ethyl acetate in hexanes to afford 4-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid 35% yield (0.25 g): MS (ES+) m/z 713.3 (M+1), 715.7 (M+1).

Workup

  1. additionwas added
  2. washThe organic phase was washed with 1 M aqueous sodium hydroxide (10 mL) and brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluting with a 25-100% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f2ecde9ee41d45f28116ea48c3b20ebc
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

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