Potassium Carbonate → 1-((5'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

HRID 1051481ノート

反応式

HRID 1051481 の反応式
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=1.Br[C:32]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:33]=1[O:39][CH3:40].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]>[Cl:38][C:36]1[CH:35]=[CH:34][C:33]([O:39][CH3:40])=[C:32]([C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([O:14][CH2:13][CH:12]([OH:30])[CH2:11][N:2]3[CH2:3][CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH2:1]3)[CH:16]=2)[CH:37]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 5219352-Bromo-4-chloroanisoleHCID 867292361-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol

生成物 1

HCID 867292621-((5'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol収率 39.5%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To a solution of 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (250 mg, 0.61 mmol) in Dioxane (3 mL) was added 2-bromo-4-chloro-1-methoxybenzene (135 mg, 0.61 mmol), 2N K2CO3 (1 mL, 2 mmol) and PdCl2(dppf)2 (20 mg, 0.025 mmol). The reaction mixture was heated at 120° C. under microwave conditions for 30 minutes before being concentrated to remove the solvents. The residue was dissolved in ethyl acetate, washed with water and the separated organic layer was dried and concentrated to yield a crude product which was purified by HPLC separation to give the title compound (102 mg, 39.5%). 1HNMR (CH3OD, 400 MHz) δ: 7.36-7.28 (m, 7H), 7.10-7.02 (m, 3H), 6.98-6.90 (m, 1H), 4.69-4.48 (m, 4H), 4.12-4.03 (m, 2H), 3.78 (s, 3H), 3.70-3.64 (m, 1H), 3.52-3.42 (m, 2H), 3.29-3.18 (m, 2H). LCMS (m/z): 424.2 [M+H]+

後処理

  1. concentrationbefore being concentrated
  2. customto remove the solvents
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water
  5. customthe separated organic layer was dried
  6. concentrationconcentrated
  7. customto yield a crude product which
  8. customwas purified by HPLC separation

出典と根拠

ORDレコード
ord-13b747d4c8494cff8b04f48e562585d7
出典データセット
uspto-grants-2016_07
特許番号
US09388173B2

反応ノート

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