1,1,1-Trimethoxybutane → 1-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol

HRID 1363579Notes

Reaction equation

HRID 1363579 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]1([OH:20])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[N:9][CH:8]=[CH:7][CH:6]=2.[C:21](OC)(OC)(OC)[CH2:22][CH2:23][CH3:24].Cl.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:22]([C:21]1[N:12]([CH2:13][C:14]2([OH:20])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]2[C:10]3[N:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=1)[CH2:23][CH3:24]

Participants

5

Reactant 3

HCID 1235121,1,1-TrimethoxybutaneHCID 10176127Pyridinium chlorideHCID 574578221-{[(3-Amino[1,5]naphthyridin-4-yl)amino]methyl}cyclohexanol

Product 1

HCID 575154271-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanolYield 70%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 1-{[(3-amino[1,5]naphthyridin-4-yl)amino]methyl}cyclohexanol (prepared as described in Part B, 15.1 mmol), trimethyl orthobutyrate (2.63 mL, 16.6 mmol), and pyridine hydrochloride (0.650 g, 5.64 mmol) in toluene (100 mL) was heated at reflux overnight. The solution was allowed to cool to rt, then was concentrated under reduced pressure. The residue was partitioned between chloroform (200 mL) and saturated aqueous sodium bicarbonate (75 mL). The aqueous layer was extracted with chloroform (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting solid was triturated with ethyl acetate and isolated by filtration. The filtrate was concentrated and the solid was again triturated with ethyl acetate; this procedure was repeated two more times. The white solids were combined and dried under vacuum to yield 1-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol (3.40 g, 70% over two steps).

Workup

  1. temperatureat reflux overnight
  2. concentrationwas concentrated under reduced pressure
  3. customThe residue was partitioned between chloroform (200 mL) and saturated aqueous sodium bicarbonate (75 mL)
  4. extractionThe aqueous layer was extracted with chloroform (2×50 mL)
  5. washThe combined organic layers were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting solid was triturated with ethyl acetate
  10. customisolated by filtration
  11. concentrationThe filtrate was concentrated
  12. customthe solid was again triturated with ethyl acetate
  13. customdried under vacuum

Sources & evidence

ORD record
ord-0a4c216849434cfcafbb460ea5ac4ac0
Source dataset
uspto-grants-2011_02
Patent number
US07884207B2

Reaction notes

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