Cesium carbonate → 1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-4-(1H-pyrazol-5-yl)-1H-benzimidazole

HRID 44495

反応式

HRID 44495 の反応式
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=3[Cl:20])[C:6]=2[CH:5]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[CH:3]=1.[NH:27]1[C:31](B(O)O)=[CH:30][CH:29]=[N:28]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]>[Cl:20][C:14]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:7]1[C:6]2[CH:5]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH:3]=[C:2]([C:29]3[NH:28][N:27]=[CH:31][CH:30]=3)[C:10]=2[N:9]=[C:8]1[CH3:11]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 112519791H-Pyrazole-5-boronic acidHCID 669767924-(4-bromo-1-(2,3-dichlorobenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine

生成物 1

HCID 569595351-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-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
80 °C

実験手順

A mixture of 4-bromo-1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole (prepared following the same procedure as for Example 21, 250 mg, 0.55 mmol), 1H-pyrazol-5-ylboronic acid (64 mg, 0.57 mmol), Pd(dba)2 (32 mg, 0.055 mmol), Cs2CO3 (358 mg, 1.1 mmol) and P(t-Bu)3 (10 wt % in hexane, 110 mg, 0.055 mmol) in dioxane (16 mL) and water (8 mL), was stirred at at 80° C. for 3 h under a nitrogen atmosphere. The reaction mixture was cooled and then concentrated. The resulting residue was purified by silica gel chromatography eluted with petroleum ether:EtOAc=1:1 to give the crude product (122 mg). The crude product was purified by Prep-HPLC to the pure product (72 mg, 30%), 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 2.46 (s, 3H,), 3.12-3.14 (m, 4H), 3.73-3.76 (m, 4H), 5.57 (s, 2H), 6.36 (d, 1H, J=7.8 Hz), 6.97 (s, 1H), 7.20-7.28 (m, 2H), 7.37 (s, 1H), 7.53-7.61 (m, 2H), 13.17 (s, 1H); LC-MS: m/e=442 [M+1]+

後処理

  1. customprepared
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated
  4. customThe resulting residue was purified by silica gel chromatography
  5. washeluted with petroleum ether

出典と根拠

ORDレコード
ord-bd35756ae84b484589e4878408bd7c1f
出典データセット
uspto-grants-2013_09
特許番号
US08541411B2

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