Potassium Carbonate → (S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-phenyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one

HRID 1354650ノート

反応式

HRID 1354650 の反応式
[CH2:1]([C@H:8]([NH:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[C:32]=1[C:38]1[NH:42][C:41]2[CH:43]=[C:44](Br)[CH:45]=[C:46]([CH3:47])[C:40]=2[N:39]=1)[CH2:9][O:10]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:49]1(B(O)O)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([C@H:8]([NH:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[C:32]=1[C:38]1[NH:42][C:41]2[CH:43]=[C:44]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH:45]=[C:46]([CH3:47])[C:40]=2[N:39]=1)[CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 136365126(S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazole-2-yl]-1H-pyridin-2-one

生成物 1

HCID 136118017(S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-phenyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one収率 52.4%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazole-2-yl]-1H-pyridin-2-one (50 mg, 0.072 mmol), phenylboronic acid (13 mg, 0.11 mmol), and 2 M K2CO3 (0.108 mL, 0.22 mmol) in THF (5 mL) was added Pd(PPh3)4 (8.3 mg, 0.007 mmol). The mixture was heated to reflux 14 h. Upon cooling, the reaction mixture was diluted with CH2Cl2, washed with saturated NaHCO3, dried over Na2SO4, and concentrated in vacuo. The residue was used for the next step without purification. LCMS (M+H)+ m/z 693 (t=2.82 min.). The crude product was treated with 4 N HCl dioxane solution (5 mL) at room temperature for 6 h. After concentration in vacuo, the residue was purified by prep. HPLC to yield the title compound (17 mg, 34%) as a white solid. 1H NMR (300 MHz, CD3OD) δ7.13–7.67 (13H, m), 6.15 (1H, d, J=7.4 Hz), 3.99–4.11 (1H, m), 3.74–3.77 (2H, m), 3.16 (1H, dd, J=5.4, 13.6 Hz), 2.97 (1H, dd, J=7.8, 13.6 Hz), 2.69 (3H, s). LCMS (M+H)+ m/z 451 (t=2.04 min.).

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux 14 h
  3. temperatureUpon cooling
  4. washwashed with saturated NaHCO3
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was used for the next step without purification
  8. customLCMS (M+H)+ m/z 693 (t=2.82 min.)
  9. additionThe crude product was treated with 4 N HCl dioxane solution (5 mL) at room temperature for 6 h
  10. concentrationAfter concentration in vacuo
  11. customthe residue was purified by prep

出典と根拠

ORDレコード
ord-9d242f7890a440abad31fe9ceb4f4b83
出典データセット
uspto-grants-2007_05
特許番号
US07223757B2

反応ノート

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