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

HRID 1429586노트

반응식

HRID 1429586 반응식
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

참가 물질

7

반응물 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)-benzothiazole2회

생성물 1

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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 312751,4-Dioxane용매

반응 조건

온도
95 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-38e3408fca9d4153b1e1ec95e62873c1
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940716B2

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