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

HRID 1429586Notes

Reaction equation

HRID 1429586 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)-benzothiazole2×

Product 1

HCID 67468425tert-butyl 4-(2-(piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 87%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

To a degassed mixture of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (Compound 1B, 400 mg, 1.277 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (987 mg, 3.19 mmol) and K2CO3 (706 mg, 5.11 mmol) in dioxane (20 mL) and water (6.67 mL) was added Pd(PPh3)4 (148 mg, 0.128 mmol) and the resulting mixture was heated at 95° C. for 3.5 h. The mixture was cooled to room temperature, diluted with water (15 mL), and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried (Na2SO4), and evaporated. The crude product was purified by column chromatography (silica gel, CH2Cl2-MeOH gradient 0 to 15% MeOH) to afford Compound 50A (460.7 mg, 1.109 mmol, 87% yield) as a light yellow solid. LCMS (m/z)=416 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with EtOAc (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe crude product was purified by column chromatography (silica gel, CH2Cl2-MeOH gradient 0 to 15% MeOH)

Sources & evidence

ORD record
ord-38e3408fca9d4153b1e1ec95e62873c1
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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