Cesium carbonate → 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-4-(1H-pyrazol-5-yl)-1H-benzimidazole

HRID 44487

反応式

HRID 44487 の反応式
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:5]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:3]=1.[NH:29]1[C:33](B(O)O)=[CH:32][CH:31]=[N:30]1.C([O-])([O-])=O.[Cs+].[Cs+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:11][C:8]1[N:7]([CH2:12][C:13]2[C:22]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:16]=[CH:15][CH:14]=2)[C:6]2[CH:5]=[C:4]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:3]=[C:2]([C:31]3[NH:30][N:29]=[CH:33][CH:32]=3)[C:10]=2[N:9]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 112519791H-Pyrazole-5-boronic acidHCID 669770504-bromo-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole

生成物 1

HCID 569595332-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-4-(1H-pyrazol-5-yl)-1H-benzimidazole

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 4-bromo-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole (200 mg, 0.46 mmol), 1H-pyrazol-5-ylboronic acid (100 mg, 0.92 mmol), Pd(dba)2 (40 mg, 0.046 mmol), Cs2CO3 (300 mg, 0.92 mmol) and P(t-Bu)3 (10 wt % in hexane, 20 mg, 0.092 mmol) in dioxane (20 mL) and water (10 mL), was stirred at 100° C. for 18 h under a nitrogen atmosphere. The reaction mixture was cooled and then concentrated. The resulting residue was purified by silica gel chromatography eluted with EtOAc to give the product (140 mg 72%), as a white solid. 1H NMR showed this compound is in a form of tautomeric mixture (major tautomer/minor tautomer=5/3) 1H NMR of the major tautomer (300 MHz, DMSO-d6) δ ppm 2.45 (s, 3H), 3.08 (s, 4H), 3.71 (s, 4H), 6.00 (s, 2H), 6.37 (d, 1H, J=7.2 Hz), 6.96 (s, 1H), 7.24-7.72 (m, 6H), 7.83-7.87 (m, 1H), 8.01 (d, 1H, J=7.2 Hz), 8.25 (d, 1H, J=4.2 Hz), 13.24 (br s, 1H); LC-MS: m/e=424 [M+1]+

後処理

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated
  3. customThe resulting residue was purified by silica gel chromatography
  4. washeluted with EtOAc
  5. customto give the product (140 mg 72%)

出典と根拠

ORDレコード
ord-80df6bc6513e44e0aac1ed53c86459f0
出典データセット
uspto-grants-2013_09
特許番号
US08541411B2

関連ノート

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