Sodium Hydroxide → N-[5-[4-(5-{[(2R,6R)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide

HRID 520645Notes

Reaction equation

HRID 520645 reaction equation
Cl[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2S(C2C=CC=CC=2)(=O)=O)=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][C@@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.[CH3:34][O:35][C:36]1[C:41]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][N:37]=1.C(=O)(O)[O-].[Na+].[OH-].[Na+]>O1CCOCC1.O>[CH3:32][C@H:30]1[O:29][C@H:28]([CH3:33])[CH2:27][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:39]4[CH:40]=[C:41]([NH:42][S:43]([CH3:46])(=[O:44])=[O:45])[C:36]([O:35][CH3:34])=[N:37][CH:38]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][NH:8]4)=[N:24][CH:23]=2)[CH2:31]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 59564698N-(2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamideHCID 595647026-Chloro-4-(5-{[(2R,6R)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 49784004N-[5-[4-(5-{[(2R,6R)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamideYield 37.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 6-chloro-4-(5-{[(2R,6R)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (109.5 mg, 0.225 mmol), N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (148 mg, 0.450 mmol) and sodium bicarbonate (56.7 mg, 0.675 mmol) in 1,4-Dioxane (5 mL) and Water (1.5 mL) stirred in air at room temp was added solid Solvias Catalyst (12.60 mg, 0.022 mmol). The reaction mixture was stirred at 120° C. for 2 hr. After this time, sodium hydroxide solution (2N, 0.5 mL) was added and the reaction mixture left to stir at room temperature for two hours. On cooling, the reaction mixture was passed through a celite cartridge (10 g) and washed with ethyl acetate. The resulting solution was evaporated and the crude residue purified by MDAP (Method J). Appropriate fractions were combined and concentrated in vacuo to afford the title compound (43 mg).

Workup

  1. waitthe reaction mixture left
  2. stirringto stir at room temperature for two hours
  3. temperatureOn cooling
  4. washwashed with ethyl acetate
  5. customThe resulting solution was evaporated
  6. customthe crude residue purified by MDAP (Method J)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b9476fde101948319f8f349a76e83e20
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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