Ethanolamine → 5-(5-(1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile

HRID 1053756노트

반응식

HRID 1053756 반응식
O[CH:2]1[C:10]2[C:5](=[C:6]([C:11]3[O:15][C:14]([C:16]4[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=4)[C:21]#[N:22])=[N:13][CH:12]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.S(Cl)(Cl)=O.C(NCC)(C)C.[CH2:38]([CH2:40][NH2:41])[OH:39]>C(Cl)Cl>[OH:39][CH2:38][CH2:40][NH:41][CH:2]1[C:10]2[C:5](=[C:6]([C:11]3[O:15][C:14]([C:16]4[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=4)[C:21]#[N:22])=[N:13][CH:12]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1

참가 물질

6

반응물 4

HCID 700EthanolamineHCID 24386Thionyl ChlorideHCID 88318IsopropylethylamineHCID 583549555-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile

생성물 1

HCID 583550735-(5-(1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile수율 62%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Prepared using General Procedure 14. To a stirring solution of 5-(5-(1-hydroxy-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile 56 (50 mg, 0.1 mmol) in DCM (3 mL) was added thionyl chloride (25 mg, 0.21 mmol) at 0° C. The reaction mixture was stirred at room temperature for 3 h. The solvent was evaporated and the crude chloride re-dissolved in dimethyl acetamide (3 mL). Isopropyl ethylamine (40.8 mg, 0.316 mmol) and ethanolamine (19.3 mg, 0.31 mmol) were added and the reaction mixture heated at 70° C. overnight. The reaction mixture was quenched with NaHCO3 and extracted with EA. The combined organic extracts were washed with brine and then dried over MgSO4. The product was purified by chromatography (10% MeOH/DCM) to afford 25 mg (60%) of 5-(5-(1-(2-hydroxyethylamino)-2,3-dihydro-1H-inden-4-yl)oxazol-2-yl)-2-isopropoxybenzonitrile 57. LCMS-ESI (m/z) calculated for C24H25N3O3: 403.5; found 404.1 [M+H]+, tR=2.41 min. 1H NMR (400 MHz, DMSO) δ 8.18 (t, J=2.3 Hz, 1H), 8.08 (dd, J=9.0, 2.3 Hz, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.44 (d, J=17.4 Hz, 1H), 7.42-7.32 (m, 1H), 7.30-7.11 (m, 2H), 4.70 (dt, J=12.2, 6.1 Hz, 2H), 4.39 (s, 1H), 3.40 (t, J=5.0 Hz, 2H), 3.18-2.95 (m, 2H), 2.93-2.75 (m, 1H), 2.73-2.54 (m, 2H), 2.38-2.16 (m, 1H), 1.98-1.78 (m, 1H), 1.15 (d, J=6.0 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 161.35, 159.17, 151.04, 146.60, 139.78, 132.16, 127.43, 125.59, 125.07, 123.99, 120.49, 116.10, 113.90, 103.77, 72.60, 62.95, 61.51, 48.70, 33.27, 31.29, 29.91, 22.02.

후처리

  1. customPrepared
  2. customThe solvent was evaporated
  3. dissolutionthe crude chloride re-dissolved in dimethyl acetamide (3 mL)
  4. temperaturethe reaction mixture heated at 70° C. overnight
  5. customThe reaction mixture was quenched with NaHCO3
  6. extractionextracted with EA
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. customThe product was purified by chromatography (10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-bcc6a006cbd34d3997ad04afab24a2b2
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394264B2

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