Morpholine → (S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one

HRID 1354651ノート

反応式

HRID 1354651 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.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+].O1CCOCC1.Cl>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:45]=[C:46]([CH3:47])[C:40]=2[N:39]=1)[CH2:9][OH:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

9

反応物 5

HCID 8083MorpholineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 204431481,4-Dioxane hydrochlorideHCID 23676156Sodium t-butoxideHCID 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 136191255(S)-4-(1-Benzyl-2-hydroxy-ethylamino)-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one収率 18.1%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

A mixture of (S)-4-(1-benzyl-2-trityloxy-ethylamino)-3-[6-bromo-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one (150 mg, 0.216 mmol), morpholine (28.2 mg, 0.324 mmol), palladium acetate (2.4 mg, 0.01 mmol), tri-tert-buylphosphine (4.4 mg. 0.02 mmol), and sodium tert-butoxide (104 mg, 1.08 mmol) in toluene (5 mL) was heated to 100° C. for 14 h under nitrogen. The reaction mixture was cooled to room temperature and diluted with EtOAc. After extraction, the combined organic layers were washed with water, brine, dried over Na2SO4. Concentration gave a brownish residue, which was treated with 4 N HCl dioxane solution (3 mL) at room temperature for 6 h. After removal of the solvent, the residue was purified by prep. HPLC to yield the title compound (18 mg, 18%). 1H NMR (400 MHz, CD3OD) δ 7.59 (1H, s), 7.12–7.28 (7H, m), 6.12 (1H, d, J=7.6 Hz), 4.01–4.08 (5H, m), 3.76 (1H, dd, J=4.8, 11.1 Hz), 3.71 (1H, dd, J=5.2, 11.1 Hz), 3.32–3.10 (4H, m), 3.09 (1H, dd, J=5.6, 13.7 Hz), 2.92 (1H, dd, J=8.0, 13.7 Hz), 2.65 (3H, s). LCMS (M+H)+ m/z 460 (t=1.30 min.).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionAfter extraction
  3. washthe combined organic layers were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration
  6. customgave a brownish residue, which
  7. customAfter removal of the solvent
  8. customthe residue was purified by prep

出典と根拠

ORDレコード
ord-5e19c79c5009499faa5d5304a275d271
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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