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

HRID 1695784Notes

Reaction equation

HRID 1695784 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([Sn](C)(C)C)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][N:14]3S(C2C=CC=CC=2)(=O)=O)=[O:8])[N:6]=1.Br[C:33]1[CH:34]=[C:35]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])[C:36]([O:39][CH3:40])=[N:37][CH:38]=1.CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([C:33]3[CH:38]=[N:37][C:36]([O:39][CH3:40])=[C:35]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])[CH:34]=3)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][NH:14]3)=[O:8])[N:6]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 582558202-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideHCID 59860141N-(5-Bromo-2-methoxypyridin-3-yl)methanesulfonamide

Product 1

HCID 445410442-Methyl-N-(6-{6-(methyloxy)-5-[(methylsulfonyl)amino]-3-pyridinyl}-1H-indazol-4-yl)-1,3-thiazole-4-carboxamideYield 6.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

2-Methyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide (200 mg, 0.356 mmol), N-[5-bromo-2-(methyloxy)-3-pyridinyl]methanesulfonamide (120 mg, 0.428 mmol) and Pd(PPh3)4 (41 mg, 0.036 mmol) were weighed to a microwave vial. DMF (3 ml) was added and the reaction was heated in the microwave at 120° C. for 30 mins. The reaction mixture was passed through a 1 g silica cartridge (pre-conditioned with methanol), washing with methanol. The solvent was removed by blow down. The residue was dissolved in DCM and purified on the ISCO companion, using a 40 g Si cartridge, a gradient of 0-6% methanol in DCM containing 1% ammonia, over 14 mins and a 40 ml/min flow rate. LCMS showed still not pure, therefore the material was further purified by MDAP (Method E). The purified material was dissolved in IPA (3 ml) and 2M NaOH (aq, 3 ml) was added. The reaction mixture was left overnight then concentrated and acidified with 2M HCl (aq). The precipitate was filtered, re-dissolved in methanol and dried by blow down to afford the title compound (11 mg).

Workup

  1. washwashing with methanol
  2. customThe solvent was removed by blow down
  3. dissolutionThe residue was dissolved in DCM
  4. custompurified on the ISCO companion
  5. customthe material was further purified by MDAP (Method E)
  6. dissolutionThe purified material was dissolved in IPA (3 ml)
  7. addition2M NaOH (aq, 3 ml) was added
  8. waitThe reaction mixture was left overnight
  9. concentrationthen concentrated
  10. filtrationThe precipitate was filtered
  11. dissolutionre-dissolved in methanol
  12. customdried by blow down

Sources & evidence

ORD record
ord-5ad8e8943d724f3fbc9344d19643594f
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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