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

HRID 2174756

반응식

HRID 2174756 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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]+

후처리

  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%)

출처 및 근거

ORD 기록
ord-5bac20fa16054dcab6ae409c5903d7fc
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062003B2

연결된 노트

불러오는 중…