Potassium Carbonate → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(3-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2-yl)amino)propan-2-ol

HRID 1399901노트

반응식

HRID 1399901 반응식
Br[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1.[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][NH:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][N:27]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][NH:25][C:26]1[CH:31]=[C:30]([C:2]2[N:7]=[C:6]3[N:8]([CH3:11])[CH:9]=[N:10][C:5]3=[CH:4][CH:3]=2)[CH:29]=[CH:28][N:27]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 232983575-bromo-3-methyl-3H-imidazo[4,5-b]pyridineHCID 867292911-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol

생성물 1

HCID 867292921-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(3-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2-yl)amino)propan-2-ol수율 26.7%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매

실험 절차

A mixture of 5-bromo-3-methyl-3H-imidazo[4,5-b]pyridine (100 mg, 0.47 mmol), 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)amino)propan-2-ol (230 mg, 0.56 mmol), K2CO3 (195 mg, 1.41 mmol) and Pd(dppf)Cl2 (10 mg) in a solution of dioxane (4 mL) and H2O (1 mL). The mixture was stirred then 120° C. for 30 min under microwave mediated heating. After cooling, the catalyst was filtered and the filtrate concentrated and purified by Prep-HPLC to give the desired product 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4-(3-methyl-3H-imidazo[4,5-b]pyridin-5-yl)pyridin-2-yl)amino)propan-2-ol (52 mg, 26.7%). 1HNMR (CH3OD, 400 MHz) δ: 8.38-8.26 (m, 1H), 8.07-7.92 (m, 2H), 7.78-7.68 (m, 1H), 7.33-7.26 (m, 1H), 7.26-7.18 (m, 1H), 7.10-6.97 (m, 3H), 6.96-6.88 (m, 1H), 4.15-4.03 (m, 1H), 3.88 (s, 3H), 3.67 (s, 2H), 3.60-3.50 (m, 1H), 3.46-3.36 (m, 1H), 2.92-2.72 (m, 4H), 2.72-2.55 (m, 2H). LCMS (m/z): 415.2 [M+H]+

후처리

  1. temperatureAfter cooling
  2. filtrationthe catalyst was filtered
  3. concentrationthe filtrate concentrated
  4. custompurified by Prep-HPLC

출처 및 근거

ORD 기록
ord-9c9e745a3077489c8906605b210a8f0d
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906900B2

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