Phosgene → 3-(4-{[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzyl)-1-ethyl-1-phenyl-urea

HRID 1592507노트

반응식

HRID 1592507 반응식
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].CCN(C(C)C)C(C)C.[C:19](Cl)(Cl)=[O:20].[NH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:33][N:34]([CH2:45][C:46]2[C:51]([CH3:52])=[CH:50][C:49]([CH3:53])=[CH:48][N:47]=2)[CH:35]2[C:44]3[N:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:38][CH2:37][CH2:36]2)=[C:29]([CH2:31][OH:32])[CH:30]=1>C1(C)C=CC=CC=1.CN(C=O)C>[CH3:52][C:51]1[C:46]([CH2:45][N:34]([CH2:33][C:28]2[CH:27]=[CH:26][C:25]([CH2:24][NH:23][C:19](=[O:20])[N:3]([CH2:1][CH3:2])[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)=[CH:30][C:29]=2[CH2:31][OH:32])[CH:35]2[C:44]3[N:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:38][CH2:37][CH2:36]2)=[N:47][CH:48]=[C:49]([CH3:53])[CH:50]=1

참가 물질

7

반응물 4

HCID 6371PhosgeneHCID 7670N-EthylanilineHCID 81531Diisopropylethylamine2회HCID 67271935(5-Aminomethyl-2-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenyl)-methanol

생성물 1

HCID 672721823-(4-{[(3,5-Dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzyl)-1-ethyl-1-phenyl-urea수율 78.8%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of N-ethylaniline (23 μL, 0.18 mmol) in toluene (3 mL) was added DIPEA (63 μL, 0.36 mmol) and phosgene (99 μL, 2.2M in toluene, 0.22 mmol). The mixture was stirred for 2 hours at room temperature under N2 and then the solvent was removed under reduced pressure to give a white solid. A solution of (5-aminomethyl-2-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-phenyl)-methanol (0.075 g, 0.18 mmol) and DIPEA (63 μL, 0.36 mmol) in DMF (4 mL) was added to the white residue and the resulting mixture was stirred for 16 hours. The solvent was removed under reduced pressure and the resulting residue was suspended in CH2Cl2 (30 mL) and quenched with saturated aqueous NaHCO3 (30 mL). The mixture was extracted with CH2Cl2 (3×30 mL) and the combined organic extracts were washed with brine (3×20 mL) and then dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 93:5:2, v/v/v) afforded 3-(4-{[(3,5-dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-3-hydroxymethyl-benzyl)-1-ethyl-1-phenyl-urea as a white foamy solid (0.080 g, 78%). 1H NMR (CDCl3) δ 1.10 (t, 3H, J=9.0 Hz), 1.60 (m, 1H), 1.99 (m, 1H), 2.19 (m, 2H), 2.20 (s 3H), 2.24 (s, 3H), 2.64 (m, 1H), 2.78 (m, 1H), 3.63 (d, 2H, J=12.0 Hz), 3.70-3.79 (m, 3H), 3.86 (t, 1H, J=7.5 Hz), 4.11 (m, 2H), 4.31 (d+m, 2H), 4.42 (m, 1H), 7.05 (m, 2H), 7.14-7.38 (m, 9H), 8.15 (s, 1H), 8.37 (d, 1H, J=3.0 Hz). HPLC: 99%.

후처리

  1. customthe solvent was removed under reduced pressure
  2. customto give a white solid
  3. stirringthe resulting mixture was stirred for 16 hours
  4. customThe solvent was removed under reduced pressure
  5. customquenched with saturated aqueous NaHCO3 (30 mL)
  6. extractionThe mixture was extracted with CH2Cl2 (3×30 mL)
  7. washthe combined organic extracts were washed with brine (3×20 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 93:5:2, v/v/v)

출처 및 근거

ORD 기록
ord-9e3a0ce241d54d44894f40fac56120f1
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291631B2

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