Ethyl orthoformate → HCID 57515551, compound

HRID 1363619Notes

Reaction equation

HRID 1363619 reaction equation
[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

Participants

7

Reactant 5

HCID 31214Ethyl orthoformate2×HCID 27851382,4-Dichloro-3-nitroquinolineHCID 10176127Pyridinium chlorideHCID 112758084-Chloro-3-nitroquinolineHCID 57515550Tert-butyl 4 {[(3-amino-2-chloroquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate2×

Product 1

HCID 57515551HCID 57515551, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-4a5dfed4c9704801a309465f5665e340
Source dataset
uspto-grants-2011_02
Patent number
US07884207B2

Reaction notes

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