Hydrochloric Acid → HCID 118036770, compound

HRID 1778072Notes

Reaction equation

HRID 1778072 reaction equation
[C:1](Cl)(Cl)=[O:2].C(N(CC)CC)C.CO[CH:14]([O:25]C)[C:15]1[N:24]=[C:23]2[C:18]([CH2:19][CH2:20][CH2:21][NH:22]2)=[CH:17][CH:16]=1.[Cl:27][C:28]1[C:33]([Cl:34])=[CH:32][N:31]=[C:30]([NH2:35])[CH:29]=1.Cl>C1COCC1.C(Cl)Cl>[Cl:27][C:28]1[C:33]([Cl:34])=[CH:32][N:31]=[C:30]([NH:35][C:1]([N:22]2[C:23]3[C:18](=[CH:17][CH:16]=[C:15]([CH:14]=[O:25])[N:24]=3)[CH2:19][CH2:20][CH2:21]2)=[O:2])[CH:29]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 8471TriethylamineHCID 107733044,5-Dichloropyridin-2-amineHCID 177501767-(Dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine2×

Product 1

HCID 118036770HCID 118036770, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of phosgene (20% solution in toluene, 0.186 ml, 0.353 mmol) in THF (2 ml) was added triethylamine (0.141 ml, 1.01 mmol). To the resulting white suspension was added a solution of 7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 4, 70 mg, 0.336 mmol) in THF (2 ml) drop wise. The resulting yellow suspension was stirred at room temperature for 1 h. 4,5-dichloropyridin-2-amine (65.7 mg, 0.403 mmol) in THF (1 ml) was added to the mixture and stirred at room temperature for 16 h. The reaction mixture was filtered through a silica gel plug and washed with heptanes/EtOAc 1:1 (35 ml), the filtrate was concentrated. The residue was dissolved in dioxane (1 ml) and treated with HCl (4 M in dioxane, 1 ml, 4.0 mmol). The mixture was stirred at room temperature for 2 h, diluted with DCM and quenched with saturated aqueous NaHCO3. The org. layer was collected and the water layer was extracted with DCM. The combined org. layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was dissolved in acetonitrile/NMP/TFA, filtered through a syringe filter (0.2 μm) and purified by preparative reverse phase LC-MS (RP 1). The clean fractions were combined and lyophilized to obtain the title compound as an off white solid.

Workup

  1. stirringstirred at room temperature for 16 h
  2. filtrationThe reaction mixture was filtered through a silica gel plug
  3. washwashed with heptanes/EtOAc 1:1 (35 ml)
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe residue was dissolved in dioxane (1 ml)
  6. stirringThe mixture was stirred at room temperature for 2 h
  7. customquenched with saturated aqueous NaHCO3
  8. customlayer was collected
  9. extractionthe water layer was extracted with DCM
  10. dry with materiallayers were dried over anhydrous Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe crude product was dissolved in acetonitrile/NMP/TFA
  13. filtrationfiltered through a syringe
  14. filtrationfilter (0.2 μm)
  15. custompurified by preparative reverse phase LC-MS (RP 1)

Sources & evidence

ORD record
ord-de913a4b87024df099f407e4ec89ee9c
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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