Sodium Carbonate → N-(6-furo[3,2-b]pyridin-6-yl-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

HRID 520653Notes

Reaction equation

HRID 520653 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]=[C:38]2[O:44][CH:43]=[CH:42][C:39]2=[N:40][CH:41]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:44]1[C:38]2[C:39](=[N:40][CH:41]=[C:36]([C:17]3[CH:16]=[C:15]4[C:11]([CH:12]=[N:13][NH:14]4)=[C:10]([NH:9][C:7]([C:5]4[N:6]=[C:2]([CH3:1])[S:3][CH:4]=4)=[O:8])[CH:18]=3)[CH:37]=2)[CH:42]=[CH:43]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 226028096-Bromofuro[3,2-b]pyridineHCID 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 53233429N-(6-furo[3,2-b]pyridin-6-yl-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

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 (50 mg), 6-bromofuro[3,2-b]pyridine (21 mg) and Pd(dppf)Cl2 (8 mg) were combined in a microwave vial. 1,4-Dioxane (0.5 ml) was added followed by sodium carbonate (44 mg) dissolved in water (0.5 ml). The reaction was heated in the microwave at 140° C. for 20 min. The reaction was filtered through a silica cartridge (1 g) washing with DCM:methanol (3:1). The solvent was then removed under a stream of nitrogen. The residue was dissolved in DMSO (1200 μl) and methanol (400 μl) and MDAP (method M). The product-containing fractions were left overnight, then concentrated and the residue dissolved in 1,4-dioxane:water (2 ml, 1:1, v/v) and freeze-dried. The residue was dissolved in DCM, a few drops of TFA were added and the reaction left overnight. The residue was further purified by MDAP (method K) then dried under nitrogen blowdown to give title compound, 13 mg.

Workup

  1. filtrationThe reaction was filtered through a silica cartridge (1 g)
  2. washwashing with DCM:methanol (3:1)
  3. customThe solvent was then removed under a stream of nitrogen
  4. dissolutionThe residue was dissolved in DMSO (1200 μl)
  5. concentrationconcentrated
  6. dissolutionthe residue dissolved in 1,4-dioxane
  7. dry with materialwater (2 ml, 1:1, v/v) and freeze-dried
  8. dissolutionThe residue was dissolved in DCM
  9. additiona few drops of TFA were added
  10. waitthe reaction left overnight
  11. customThe residue was further purified by MDAP (method K)
  12. customthen dried under nitrogen

Sources & evidence

ORD record
ord-994739a0823943d784ec58b3c3a6eced
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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