Sodium Carbonate → N-[6-(5-Amino-6-chloro-3-pyridinyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

HRID 1695747Notes

Reaction equation

HRID 1695747 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]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:12]=3)=[O:8])[N:6]=1.Br[C:36]1[CH:37]=[C:38]([NH2:43])[C:39]([Cl:42])=[N:40][CH:41]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>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>[NH2:43][C:38]1[CH:37]=[C:36]([C:17]2[CH:18]=[C:10]([NH:9][C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[O:8])[C:11]3[C:15]([CH:16]=2)=[N:14][N:13]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:12]=3)[CH:41]=[N:40][C:39]=1[Cl:42]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 218583543-Amino-5-bromo-2-chloropyridineHCID 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 58255741N-[6-(5-Amino-6-chloro-3-pyridinyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamideYield 45.9%

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 (0.75 g), 5-bromo-2-chloro-3-pyridinamine (0.39 g), sodium carbonate (0.66 g) and Pd(dppf)Cl2 (0.114 g) were weighed to a 10-20 ml microwave vial and 1,4-dioxane (8 ml) then water (8 ml) were added. The reaction was heated at 140° C. for 20 min. The reaction was passed through a 10 g silica cartridge, washing with methanol:DCM (1:1, v/v). The solvent was evaporated and the residue was purified on a 40 g ISCO companion silica cartridge, eluting with 1.5-7.5% methanol in DCM (containing 1% ammonia) at 40 ml/min. Pure fractions were combined and evaporated to dryness to give title compound (335 mg).

Workup

  1. washwashing with methanol:DCM (1:1
  2. customThe solvent was evaporated
  3. customthe residue was purified on a 40 g ISCO companion silica cartridge
  4. washeluting with 1.5-7.5% methanol in DCM (containing 1% ammonia) at 40 ml/min
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-a56ef88e29bf4aa580f67713d9f1918e
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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