6-Methylpyridine-2-carboxylic acid → N-(6-{6-Chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-methyl-2-pyridinecarboxamide

HRID 1695794Notes

Reaction equation

HRID 1695794 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.ClC(N(C)C)=C(C)C.[NH2:19][C:20]1[CH:28]=[C:27]([C:29]2[CH:30]=[C:31]([NH:36][S:37]([CH3:40])(=[O:39])=[O:38])[C:32]([Cl:35])=[N:33][CH:34]=2)[CH:26]=[C:25]2[C:21]=1[CH:22]=[N:23][N:24]2S(C1C=CC=CC=1)(=O)=O>C(Cl)Cl>[Cl:35][C:32]1[N:33]=[CH:34][C:29]([C:27]2[CH:26]=[C:25]3[C:21]([CH:22]=[N:23][NH:24]3)=[C:20]([NH:19][C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=3)=[O:10])[CH:28]=2)=[CH:30][C:31]=1[NH:36][S:37]([CH3:40])(=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 702826-Methylpyridine-2-carboxylic acidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 58255829N-{5-[4-Amino-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-chloro-3-pyridinyl}methanesulfonamide

Product 1

HCID 44539827N-(6-{6-Chloro-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-6-methyl-2-pyridinecarboxamideYield 41.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

6-Methyl-2-pyridinecarboxylic acid (43 mg) was dissolved in DCM (2 ml) and 1-chloro-N,N,2-trimethyl-1-propen-1-amine (0.042 ml) was added. The reaction was stirred for 15 mins. N-{5-[4-Amino-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-chloro-3-pyridinyl}methane sulfonamide (100 mg) in DCM (4 ml) was added and the reaction left at RT. The reaction was evaporated to dryness. IPA (3 ml) was added to the residue followed by 2M NaOH (aq) (3 ml) and the reaction was left overnight. The solution was neutralised using 2M HCl (aq) and then concentrated. The precipitate that formed was filtered then DMSO was added to the precipitate. Attempts to filter the solid failed so the reaction was blown down under a stream of nitrogen. The residue was redissolved in DMSO (0.5 ml) and purified by MDAP (method E). The pure fraction was evaporated to dryness to give title compound (40 mg).

Workup

  1. waitthe reaction left at RT
  2. customThe reaction was evaporated to dryness
  3. additionIPA (3 ml) was added to the residue
  4. waitthe reaction was left overnight
  5. concentrationconcentrated
  6. customThe precipitate that formed
  7. filtrationwas filtered
  8. additionDMSO was added to the precipitate
  9. filtrationto filter the solid
  10. dissolutionThe residue was redissolved in DMSO (0.5 ml)
  11. custompurified by MDAP (method E)
  12. customThe pure fraction was evaporated to dryness

Sources & evidence

ORD record
ord-af5b9c87623e461fb419fcc5f79ac653
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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