Chlorosuccinimide → HCID 44481371, compound

HRID 2067982Notes

Reaction equation

HRID 2067982 reaction equation
COC(=O)CC[S:6]([C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:26]=2[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])=[CH:11][N:10]=1)(=[O:8])=[O:7].C[O-].[Na+].[Na].ClN1C(=[O:46])CCC1=O.[O:48]1[CH2:53][CH2:52][CH:51]([NH2:54])[CH2:50][CH2:49]1>C1COCC1.CO>[O:48]1[CH2:53][CH2:52][CH:51]([NH:54][S:6]([C:9]2[N:10]=[CH:11][C:12]([CH:15]([NH:19][C:20]([C:22]3[CH:23]=[N:24][N:25]([C:28]4[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=4)[C:26]=3[CH3:27])=[O:21])[CH2:16][CH2:17][CH3:18])=[CH:13][CH:14]=2)(=[O:7])=[O:8])[CH2:50][CH2:49]1.[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([N:25]2[C:26]([CH3:27])=[C:22]([C:20]([NH:19][CH:15]([C:12]3[CH:13]=[CH:14][C:9]([S:6]([OH:7])(=[O:8])=[O:46])=[N:10][CH:11]=3)[CH2:16][CH2:17][CH3:18])=[O:21])[CH:23]=[N:24]2)=[CH:33][CH:32]=1

Participants

9

Reactant 5

HCID 31398ChlorosuccinimideHCID 4192234-AminotetrahydropyranHCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 44480866HCID 44480866, compound

Product 2

HCID 44481371HCID 44481371, compoundYield 12%HCID 44481372HCID 44481372, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (150 mg, 0.29 mmol) in anhydrous THF (15 mL) is added sodium methoxide in methanol (2.6 M solution freshly prepared by dissolving 120 mg of sodium in 2.0 mL of methanol, 0.12 mL, 0.32 mmol). After stiffing at room temperature for 15 min, the reaction mixture is concentrated in vacuo. Anhydrous THF (10 mL) is added and the concentration process is repeated. The resultant residue is dried under high vacuum for 5 min, dissolved in THF (15 mL) and treated with N-chlorosuccinimide (77 mg, 0.58 mmol). The reaction mixture is stirred at room temperature for 15 min and then tetrahydro-pyran-4-ylamine (130 mg, 1.3 mmol) is added in one portion. After 20 min the reaction mixture is concentrated in vacuo and purified directly by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive) followed preparative TLC (eluted with 70% EtOAc/hexanes) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid {1-[6-(tetrahydro-pyran-4-ylsulfamoyl)-pyridin-3-yl]-butyl}-amide (14 mg, 9%) and 5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-2-sulfonic acid (15 mg, 12%).

Workup

  1. customfreshly prepared
  2. concentrationthe reaction mixture is concentrated in vacuo
  3. additionAnhydrous THF (10 mL) is added
  4. dry with materialThe resultant residue is dried under high vacuum for 5 min
  5. dissolutiondissolved in THF (15 mL)
  6. concentrationAfter 20 min the reaction mixture is concentrated in vacuo
  7. custompurified directly by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive)
  8. washTLC (eluted with 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-57bbc3fb703a4add8100815cf268a6fc
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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