2-amino-5-(3-cyclopropylsulfamoyl-phenyl)-N-methoxy-N-methyl-nicotinamide → 3-[6-Amino-5-(4-tert-butyl-benzoyl)-pyridin-3-yl]-N-cyclopropyl-benzenesulfonamide

HRID 2387193

Reaction equation

HRID 2387193 reaction equation
[NH2:1][C:2]1[N:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20](=[O:26])(=[O:25])[NH:21][CH:22]3[CH2:24][CH2:23]3)[CH:15]=2)=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].[C:27]([C:31]1[CH:36]=[CH:35][C:34]([Mg]Br)=[CH:33][CH:32]=1)([CH3:30])([CH3:29])[CH3:28]>C1COCC1.C(Cl)Cl>[NH2:1][C:2]1[N:13]=[CH:12][C:11]([C:14]2[CH:15]=[C:16]([S:20]([NH:21][CH:22]3[CH2:23][CH2:24]3)(=[O:25])=[O:26])[CH:17]=[CH:18][CH:19]=2)=[CH:10][C:3]=1[C:4](=[O:5])[C:34]1[CH:35]=[CH:36][C:31]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:32][CH:33]=1

Participants

5

Reactant 2

HCID 866345442-amino-5-(3-cyclopropylsulfamoyl-phenyl)-N-methoxy-N-methyl-nicotinamideHCID 178440986HCID 178440986, compound

Product 1

HCID 442333443-[6-Amino-5-(4-tert-butyl-benzoyl)-pyridin-3-yl]-N-cyclopropyl-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-amino-5-(3-cyclopropylsulfamoyl-phenyl)-N-methoxy-N-methyl-nicotinamide (Intermediate GA) (0.08 g, 0.21 mmol) in THF (3 ml) is cooled to 0° C. 2M 4-tert Butyl phenyl magnesium bromide in THF (0.32 ml, 0.64 mmol) is added dropwise, and the resulting solution is stirred and allowed to warm to room temperature overnight. The reaction is quenched with 2M HCl (5 ml). The solvent is removed in vacuo and the residue purified by reverse phase column chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA). The solid obtained is dissolved in DCM, washed with 2M NaOH. The solvent is removed in vacuo and the resulting solid is dried in vacuo at 40° C. overnight to yield the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.69 (1H, d), 8.01 (1H, d), 7.97-7.89 (3H, m), 7.78 (1H, d), 7.72-7.67 (5H, m), 7.64 (2H, d), 2.18-2.13 (1H, m), 1.38 (9H, s), 0.47-0.38 (4H, m); MS m/z 450 [M+H]+

Workup

  1. customThe reaction is quenched with 2M HCl (5 ml)
  2. customThe solvent is removed in vacuo
  3. customthe residue purified by reverse phase column chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA)
  4. customThe solid obtained
  5. washwashed with 2M NaOH
  6. customThe solvent is removed in vacuo
  7. customthe resulting solid is dried in vacuo at 40° C. overnight

Sources & evidence

ORD record
ord-c016d34dcc9b434f9a7d6782d4a54f75
Source dataset
uspto-grants-2012_09
Patent number
US08268834B2

Linked notes

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