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

HRID 44742Notes

Reaction equation

HRID 44742 reaction equation
[CH2:1]([C:4]1[N:5]([CH2:17][C:18]2([OH:24])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].ClC1C=CC=C(C(OO)=O)C=1.[OH-].[NH4+:37].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[NH2:37][C:8]1[C:7]2[N:16]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:17][C:18]3([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)[C:6]=2[C:15]2[N:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 575154271-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol

Product 1

HCID 575154261-[(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanolYield 38%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol (1.43 g, 4.41 mmol) in chloroform (20 mL) at rt was added m-chloroperbenzoic acid (m-CPBA, 70%, 2.17 g, 8.82 mmol). After 1.5 h, the solution was was cooled to 0° C. and concentrated ammonium hydroxide (5 mL) was added. After 3 min, p-toluenesulfonyl chloride (TsCl, 0.920 g, 4.85 mmol) was added in portions. After 1 h, the reaction mixture was filtered and the filter cake was washed with chloroform. The filtrate was washed with saturated aqueous sodium bicarbonate (50 mL) and dried over Na2SO4, filtered, and concentrated under reduced pressure to yield an orange foam which was purified twice by HPFC (silica gel, gradient elution with 0-25% CMA/CHCl3 where CMA is a solution comprised of 80% CHCl3, 18% MeOH, and 2% conc. NH4OH; followed by 0-30% CMA/CHCl3). The appropriate fractions were concentrated and triturated with acetonitrile. The solid was isolated by filtration and dried at 100° C. under vacuum to yield 1-[(4-amino-2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol (567 mg, 38%) as a white powder, mp 209.0-211.0° C. Anal. Calcd for C19H25N5O.0.2H2O C, 66.35; H, 7.47; N, 20.36. Found: C, 66.62; H, 7.34; N, 20.05.

Workup

  1. waitAfter 3 min
  2. waitAfter 1 h
  3. filtrationthe reaction mixture was filtered
  4. washthe filter cake was washed with chloroform
  5. washThe filtrate was washed with saturated aqueous sodium bicarbonate (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto yield an orange foam which
  10. customwas purified twice by HPFC (
  11. washsilica gel, gradient elution with 0-25% CMA/CHCl3 where CMA
  12. concentrationThe appropriate fractions were concentrated
  13. customtriturated with acetonitrile
  14. customThe solid was isolated by filtration
  15. customdried at 100° C. under vacuum

Sources & evidence

ORD record
ord-521f224825cd4639a056cbede6069795
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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