Lithium Hexamethyldisilazide → 4-((4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)amino)-N-(2,4-dimethoxybenzyl)-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 1524437Notes

Reaction equation

HRID 1524437 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:4]=1[CH2:5][N:6]([C:20]1[S:24][N:23]=[CH:22][N:21]=1)[S:7]([C:10]1[CH:15]=[CH:14][C:13](F)=[C:12]([N+:17]([O-:19])=[O:18])[CH:11]=1)(=[O:9])=[O:8].[Cl:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[C:34]([C:39]2[N:43]([CH3:44])[N:42]=[CH:41][CH:40]=2)[CH:33]=1.ClC1C=CC(B(O)O)=C(C2N(C)N=CC=2)C=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>[Cl-].[NH4+].O.C1COCC1>[Cl:31][C:32]1[CH:38]=[CH:37][C:35]([NH:36][C:13]2[CH:14]=[CH:15][C:10]([S:7]([N:6]([CH2:5][C:4]3[CH:25]=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:3]=3[O:2][CH3:1])[C:20]3[S:24][N:23]=[CH:22][N:21]=3)(=[O:9])=[O:8])=[CH:11][C:12]=2[N+:17]([O-:19])=[O:18])=[C:34]([C:39]2[N:43]([CH3:44])[N:42]=[CH:41][CH:40]=2)[CH:33]=1

Participants

8

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 71258743(4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)boronic acidHCID 71259496N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide2×HCID 812750764-chloro-2-(1-methyl-1H-pyrazol-5-yl)aniline

Product 1

HCID 712594854-((4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)amino)-N-(2,4-dimethoxybenzyl)-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideYield 73.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A round-bottom flask was charged with N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (INTERMEDIATE M) (189 mg, 0.416 mmol), 4-chloro-2-(1-methyl-1H-pyrazol-5-yl)aniline (the product of STEP 1 in the preparation of INTERMEDIATE F) (95 mg, 0.457 mmol), and THF (2079 μl) to give a brown solution. The flask was cooled in an ice bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1248 μl, 1.248 mmol) was added dropwise over 1 minute to give a dark maroon mixture. After 10 min, the mixture was diluted with a saturated aq. ammonium chloride solution and water, then extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude product was purified by chromatography on silica gel (20 to 70% EtOAc/heptane) give 4-((4-chloro-2-(1-methyl-1H-pyrazol-5-yl)phenyl)amino)-N-(2,4-dimethoxybenzyl)-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (197.46 mg, 0.308 mmol, 73.9% yield) as a bright orange solid. m/z (ESI) 642.0 (M+H)+.

Workup

  1. customto give a brown solution
  2. temperatureThe flask was cooled in an ice bath for 5 min
  3. customto give a dark maroon mixture
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography on silica gel (20 to 70% EtOAc/heptane)

Sources & evidence

ORD record
ord-dc0a300a437b429cb70420cd43314505
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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