Pyridine → 2-Methyl-N-(6-{5-[(phenylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamide

HRID 1695803Notes

Reaction equation

HRID 1695803 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:12]=[C:13]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:14]=[N:15][CH:16]=2)[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2S(C1C=CC=CC=1)(=O)=O.N1C=CC=CC=1.[CH3:42][C:43]1[S:44][CH:45]=[C:46]([C:48](Cl)=[O:49])[N:47]=1>C(Cl)Cl>[CH3:42][C:43]1[S:44][CH:45]=[C:46]([C:48]([NH:1][C:2]2[CH:10]=[C:9]([C:11]3[CH:16]=[N:15][CH:14]=[C:13]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)(=[O:20])=[O:19])[CH:12]=3)[CH:8]=[C:7]3[C:3]=2[CH:4]=[N:5][NH:6]3)=[O:49])[N:47]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 211839592-Methyl-1,3-thiazole-4-carbonyl chloride3×HCID 58255758N-{5-[4-Amino-1-(phenylsulfonyl)-1H-indazol-6-yl]-3-pyridinyl}benzenesulfonamide

Product 1

HCID 445396292-Methyl-N-(6-{5-[(phenylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamideYield 22.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{5-[4-Amino-1-(phenylsulfonyl)-1H-indazol-6-yl]-3-pyridinyl}benzenesulfonamide (100 mg) was dissolved in DCM (5 ml) and pyridine (0.024 ml) was added. The reaction was stirred at RT for 2 min before 2-methyl-1,3-thiazole-4-carbonyl chloride (35 mg) was added. The reaction was stirred at RT for 18 h. Further 2-methyl-1,3-thiazole-4-carbonyl chloride (10 mg) was added and stirring continued for 2 h at RT. Further 2-methyl-1,3-thiazole-4-carbonyl chloride (35 mg) was added and the reaction stirred at RT for 18 h before being quenched with water. DCM was added and the reaction was passed through a hydrophobic frit and evaporated to dryness. The residue was dissolved in DMSO:MeOH (1:1, v/v, 1 ml) and purified by MDAP (method E). The desired dried intermediate was dissolved in MeOH and 2M NaOH (1 ml) was added. The reaction was stirred at RT for 30 min. The reaction was neutralised with 2M HCl (aq) then evaporated to dryness. The residue was dissolved in MeOH and loaded onto a SCX-2 SPE cartridge pre-conditioned with MeOH. After eluting with MeOH then 10% NH3 in MeOH, the basic fraction was evaporated to dryness to give the title compound (22 mg).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitcontinued for 2 h at RT
  4. stirringthe reaction stirred at RT for 18 h
  5. custombefore being quenched with water
  6. additionDCM was added
  7. customevaporated to dryness
  8. dissolutionThe residue was dissolved in DMSO:MeOH (1:1, v/v, 1 ml)
  9. custompurified by MDAP (method E)
  10. dissolutionwas dissolved in MeOH
  11. addition2M NaOH (1 ml) was added
  12. stirringThe reaction was stirred at RT for 30 min
  13. customthen evaporated to dryness
  14. dissolutionThe residue was dissolved in MeOH
  15. washAfter eluting with MeOH
  16. custom10% NH3 in MeOH, the basic fraction was evaporated to dryness

Sources & evidence

ORD record
ord-5a8391a6d92b44dbbe4641873940aa5f
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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