Hydrochloric Acid → 5-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

HRID 1520072노트

반응식

HRID 1520072 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]1[N:12]=[N:13][N:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[O:23])=[CH:18][CH:17]=2)[CH:15]=1.[CH2:30]([N:37]1[CH2:42][CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH2:39][CH2:38]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[CH2:30]([N:37]1[CH2:38][CH:39]=[C:40]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][N:6]=[C:5]3[C:11]2[N:12]=[N:13][N:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)=[O:23])=[CH:18][CH:17]=3)[CH:15]=2)[CH2:41][CH2:42]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 497592141-Benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1,2,3,6-tetrahydropyridineHCID 574046585-bromo-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

생성물 1

HCID 680610495-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
150 °C

실험 절차

A suspension of {4-[4-(5-Bromo-1H-indazol-3-yl)-[1,2,3]triazol-1-yl]-phenyl}-morpholin-4-yl-methanone (100 mg; 0.22 mmol; 1.0 eq.), 1-Benzyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,3,6-tetrahydro-pyridine; hydrochloride (J&W Pharm Lab, 222 mg; 0.66 mmol; 3.00 eq.), Pd2Cl2(PPh3)2(15 mg; 0.02 mmol; 0.1 eq.), potassium carbonate (91 mg; 0.66 mmol; 3.0 eq.) in dioxane (2 mL) and water (1 mL) was degassed with nitrogen flow and heated in MW at 150° C. for 10 min. The reaction mixture was filtered through a celite pad, water was added to the filtrate. Aqueous phase was extracted three times with DCM using separators tubes. Combined organic phases were concentrated under reduced pressure and the crude was purified by flash chromatography on silica (DCM/MeOH, gradient from 100:0 to 90:10) to give the title compound as yellow powder. 1H NMR (300 MHz, DMSO-d6) δ 13.37 (brs, 1H), 9.39 (s, 1H), 8.30 (s, 1H), 8.22-8.10 (m, 2H), 7.76-7.65 (m, 2H), 7.65-7.50 (m, 2H), 7.42-7.31 (m, 4H), 7.31-7.22 (m, 1H), 6.30-6.10 (m, 1H), 3.78-3.50 (m, 8H), 3.47-3.37 (m, 2H), 3.18-3.07 (m, 2H), 2.77-2.56 (m, 4H). HPLC (Condition A): Rt 2.87 min (purity 97.5%). MS (ESI+): 546.4, MS (ESI−): 544.3.

후처리

  1. filtrationThe reaction mixture was filtered through a celite pad, water
  2. additionwas added to the filtrate
  3. extractionAqueous phase was extracted three times with DCM using separators tubes
  4. concentrationCombined organic phases were concentrated under reduced pressure
  5. customthe crude was purified by flash chromatography on silica (DCM/MeOH, gradient from 100:0 to 90:10)

출처 및 근거

ORD 기록
ord-9e6e8d82695e47b89b0418005b158062
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073892B2

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