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

HRID 1793744노트

반응식

HRID 1793744 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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) δ 7.13–7.67 (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.).

후처리

  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

출처 및 근거

ORD 기록
ord-4ae23718e7aa4596a65986ea647e0ce5
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07081454B2

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