Hydrochloric Acid → 1-[(S)-1-Benzyl-2-(2-pyrrolidin-1-yl-ethylamino)-ethyl]-3-(4-phenoxy-phenyl)-urea

HRID 1271004ノート

反応式

HRID 1271004 の反応式
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:35])[NH:16][C@@H:17]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:18]([NH:20][CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC(OC2C=CC(NC(=S)N[C@@H](CC3C=CC=CC=3)C(NCCN3CCCC3)=O)=CC=2)=CC=1.Cl.O1CCOCC1.O(C1C=CC(N=C=O)=CC=1)C1C=CC=CC=1>C(Cl)Cl.CCOC(C)=O>[CH2:28]([C@H:17]([NH:16][C:15]([NH:14][C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:12]=1)=[O:35])[CH2:18][NH:20][CH2:21][CH2:22][N:23]1[CH2:24][CH2:25][CH2:26][CH2:27]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 27348964-Phenoxyphenyl isocyanateHCID 58843147(S)-2-{3-[4-(4-Chloro-phenoxy)-phenyl]-thioureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamideHCID 69432798(S)-2-[3-(4-Phenoxy-phenyl)-ureido]-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide

生成物 1

HCID 588431781-[(S)-1-Benzyl-2-(2-pyrrolidin-1-yl-ethylamino)-ethyl]-3-(4-phenoxy-phenyl)-urea収率 25%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(S)-2-[3-(4-Phenoxy-phenyl)-ureido]-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide. To a solution of [(S)-2-phenyl-1-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester (Example 9, step A) (0.1 g, 0.28 mmol) in CH2Cl2 (3 mL), a 4 M solution of HCl in dioxane (2.5 mL, 10 mmol) was added, and the mixture was stirred for 4 h at rt. The solvents were removed, and the residue was treated with CH2Cl2. The solvents were removed again under reduced pressure. The residue was dissolved in CH2Cl2 (3 mL), and TEA (0.07 g, 0.69 mmol) was added at 0° C. followed by 4-phenoxyphenylisocyanate (0.07 g, 0.33 mmol). The mixture was warmed to rt over a period of 4 h and then diluted with EtOAc (75 mL). The organic layer was washed with saturated NaHCO3 (25 mL) and brine (25 mL), and dried (Na2SO4). The solvent was removed, and the residue was purified by flash column chromatography using 0–20% MeOH (1% NH4OH)/CH2Cl2 to afford 0.03 g (25%) of the desired product. MS (electrospray): mass calculated for C28H32N4O3, 472.25; m/z found, 473.2 [M+H]+, 495.2 [M+Na]+. 1H NMR (400 MHz, DMSO-d6): 8.68 (s, 1H), 8.04 (t, J=5.5 Hz, 1H), 7.36–6.89 (m, 14H), 6.30 (d, J=8.3 Hz, 1H), 4.46 (m, 1H), 3.15 (m, 2H), 2.96 (dd, J=13.6, 5.6 Hz, 1H), 2.82 (dd, J=13.6, 7.7 Hz, 1H), 2.42–2.37 (m, 6H), 1.67–1.63 (m, 4H).

後処理

  1. customThe solvents were removed
  2. additionthe residue was treated with CH2Cl2
  3. customThe solvents were removed again under reduced pressure
  4. dissolutionThe residue was dissolved in CH2Cl2 (3 mL)
  5. temperatureThe mixture was warmed to rt over a period of 4 h
  6. washThe organic layer was washed with saturated NaHCO3 (25 mL) and brine (25 mL)
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was removed
  9. customthe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-46551ea091544219ae0fba89e4cf81c3
出典データセット
uspto-grants-2007_04
特許番号
US07202269B2

反応ノート

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