Ethyl orthoformate → HCID 57515551, 화합물

HRID 44781

반응식

HRID 44781 반응식
[NH2:1][C:2]1[C:3]([Cl:28])=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]1([OH:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:30]1C([N+]([O-])=O)=C(Cl)C2C(=CC=CC=2)N=1.ClC1C2C(=CC=CC=2)N=CC=1[N+]([O-])=O.Cl.N1C=CC=CC=1.C(OC(OCC)OCC)C>C1(C)C=CC=CC=1>[Cl:28][C:3]1[C:2]2[N:1]=[CH:30][N:12]([CH2:13][C:14]3([OH:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][CH2:15]3)[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1

참가 물질

7

반응물 5

HCID 31214Ethyl orthoformate2회HCID 27851382,4-Dichloro-3-nitroquinolineHCID 10176127Pyridinium chlorideHCID 112758084-Chloro-3-nitroquinolineHCID 57515550HCID 57515550, 화합물2회

생성물 1

HCID 57515551HCID 57515551, 화합물

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

Under a nitrogen atmosphere, tert-butyl 4 {[(3-amino-2-chloroquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate (0.25 g, 0.61 mmol, prepared according to the general methods of Example 4 Parts A through D using 2,4-dichloro-3-nitroquinoline in lieu of 4-chloro-3-nitroquinoline in Part C), toluene (5 mL), pyridine hydrochloride (0.02 g), and triethylorthoformate (0.11 mL, 0.65 mmol) was heated at reflux for 2 hours. More triethylorthoformate (0.5 eq) was added and the reaction mixture was heated for an additional hour. The reaction was rerun in the same manner using 5.25 g of tert-butyl 4 {[(3-amino-2-chloroquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate. The small and larger scale reaction mixtures were combined and washed with water (50 mL). The aqueous layer was extracted with dichloromethane (2×100 mL). The organic layers were combined and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel eluting with a gradient of 0-10% methanol in ethyl acetate) to provide 4.08 g of tert-butyl 4-[(4-chloro-1H-imidazo[4,5-c]quinolin-1-yl)methyl]-4-hydroxypiperidine-1-carboxylate as a tan frothy solid.

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperaturethe reaction mixture was heated for an additional hour
  4. customThe small and larger scale reaction mixtures
  5. washwashed with water (50 mL)
  6. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (silica gel eluting with a gradient of 0-10% methanol in ethyl acetate)

출처 및 근거

ORD 기록
ord-0c4daffce4da4e3c88a0b888541fc707
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541438B2

연결된 노트

불러오는 중…