Acetonitrile → 2-Methyl-N-[6-(3-pyridinyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 1695771Notes

Reaction equation

HRID 1695771 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[C:11]3[C:15]([CH:16]=[C:17](B4OC(C)(C)CC(C)(C)O4)[CH:18]=2)=[N:14][N:13](C2CCCCO2)[CH:12]=3)=[O:8])[N:6]=1.Br[C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1.[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].CC#N>O1CCOCC1.O.Cl[Pd]C1C=CC=CC=1C1C=CC=CC=1N(C)C.[C@H]12C[C@H](CC1)CC2PC1C[C@H]2C[C@@H]1CC2>[CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:18]=[C:17]([C:36]3[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=3)[CH:16]=[C:15]3[C:11]=2[CH:12]=[N:13][NH:14]3)=[O:8])[N:6]=1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 122863-BromopyridineHCID 61695Pentapotassium TriphosphateHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Product 1

HCID 445404852-Methyl-N-[6-(3-pyridinyl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamideYield 11.9%

Reagents, catalysts & solvents 3

HCID 178420574HCID 178420574, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

2-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (53 mg, 0.11 mmol) was dissolved in 1,4-Dioxane (0.4 ml) and added to 3-bromopyridine (16 mg, 0.1 mmol) in a microwave vessel. 1,4-Dioxane (0.4 ml) was added, followed by chloro[2′-(dimethylamino)-2-biphenylyl]palladium-(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (1:1) (Solvias catalyst, 2 mg, 0.004 mmol, (heaped microspatula) available from ABCR) and a solution of potassium triphosphate (0.2 g, 0.1 mmol) in water (0.2 ml). The vessel was sealed and heated in CEM Discover using initial 150 W to 110° C. for 20 min. After cooling the solution was loaded onto a C18 SPE cartridge (pre-conditioned with MeCN/0.1% TFA) and flushed through with a further 3 ml MeCN/0.1% TFA. Solvent was removed by blowdown under a stream of nitrogen. The residue was dissolved in MeOH (0.5 ml) and loaded onto a SCX-2 SPE cartridge (1 g) pre-conditioned with MeOH. The material was left on the column for 1 hr then eluted with 2M ammonia/MeOH and evaporated to dryness. The sample was purified by MDAP (Method C) to afford the title compound (4 mg).

Workup

  1. customThe vessel was sealed
  2. temperatureheated in CEM Discover
  3. customfor 20 min
  4. temperatureAfter cooling the solution
  5. customflushed through with a further 3 ml MeCN/0.1% TFA
  6. customSolvent was removed by blowdown under a stream of nitrogen
  7. dissolutionThe residue was dissolved in MeOH (0.5 ml)
  8. washthen eluted with 2M ammonia/MeOH
  9. customevaporated to dryness
  10. customThe sample was purified by MDAP (Method C)

Sources & evidence

ORD record
ord-fcd8d9203335479d9b7aba4a6f943e44
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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