Potassium Carbonate → tert-butyl 4-(2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1429557노트

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HRID 1429557 반응식
Br[C:2]1[CH:23]=[CH:22][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][N:13]([C:16]4[S:17][C:18]([CH3:21])=[N:19][N:20]=4)[CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=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>[CH3:21][C:18]1[S:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([O:9][C:7]3[S:8][C:4]4[CH:3]=[C:2]([C:32]5[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=5)[CH:23]=[CH:22][C:5]=4[N:6]=3)[CH2:11][CH2:12]2)=[N:20][N:19]=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 674670296-Bromo-2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazole

생성물 1

HCID 67468486tert-butyl 4-(2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate수율 79%

시약·촉매·용매 3

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

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온도
100 °C

실험 절차

To a degassed solution of 6-bromo-2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazole (450 mg, 1.094 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (406 mg, 1.313 mmol) and potassium carbonate (454 mg, 3.28 mmol) in dioxane (9 mL) and water (3.0 mL) was added Pd(Ph3P)4 (63 mg, 0.055 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was cooled to rt, diluted with water (20 mL), and extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 30 to 100% EtOAc) to afford tert-butyl 4-(2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate (443 mg, 0.862 mmol, 79% yield) as a yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 7.59-7.65 (2H, m), 7.41 (1H, dd, J=8.5, 1.7 Hz), 6.00-6.11 (1H, m), 5.41-5.48 (1H, m), 4.07-4.12 (2H, m), 3.75-3.83 (2H, m), 3.66 (2H, t, J=5.5 Hz), 3.52-3.59 (2H, m), 2.60 (3H, s), 2.53-2.58 (2H, m), 2.19-2.27 (2H, m), 2.06-2.14 (2H, m), 1.50 (9H, s). LCMS (m/z)=514 (M+H)+.

후처리

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with CH2Cl2 (3×15 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, hexanes-EtOAc gradient 30 to 100% EtOAc)

출처 및 근거

ORD 기록
ord-5de548f5edef4d55a55a6d778c60c5b0
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940716B2

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