Potassium Carbonate → tert-butyl 4-(2-(piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1429576Notes

Reaction equation

HRID 1429576 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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>[NH:13]1[CH2:14][CH2:15][CH:10]([O:9][C:7]2[S:8][C:4]3[CH:3]=[C:2]([C:26]4[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]=4)[CH:17]=[CH:16][C:5]=3[N:6]=2)[CH2:11][CH2:12]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 674668246-Bromo-2-(piperidin-4-yloxy)-benzothiazole

Product 1

HCID 67468425tert-butyl 4-(2-(piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 87.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (800 mg, 2.55 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.185 g, 3.83 mmol) and potassium carbonate (1.412 g, 10.22 mmol) in dioxane (21 mL) and water (7 mL) was added Pd(Ph3P)4 (148 mg, 0.128 mmol). The reaction mixture was stirred at 100° C. overnight. The mixture was cooled to rt, diluted with water (60 mL), and extracted with CH2Cl2 (3×30 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, CH2Cl2-MeOH gradient 0 to 20% MeOH) to afford tert-butyl 4-(2-(piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (923 mg, 2.221 mmol, 87% yield) as a white foam. LCMS (m/z)=416 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. extractionextracted with CH2Cl2 (3×30 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica gel, CH2Cl2-MeOH gradient 0 to 20% MeOH)

Sources & evidence

ORD record
ord-1f420a8354524ec2a7f7ca9e1320c39b
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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