Butanal → N-[2-[3-(Butylamino)propyl]-6-chloro-5-quinolinyl]-cyclohexaneacetamide dihydrochloride

HRID 2217818Notes

Reaction equation

HRID 2217818 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[C:11]=2[NH:15][C:16](=[O:24])[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:6]=1.[CH:26](=O)[CH2:27][CH2:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O1CCCC1>[ClH:25].[ClH:25].[CH2:26]([NH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[C:11]=2[NH:15][C:16](=[O:24])[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:6]=1)[CH2:27][CH2:28][CH3:29]

Participants

6

Reactant 3

HCID 261ButanalHCID 5049666Sodium triacetoxyborohydrideHCID 11268393N-[2-(3-Aminopropyl)-6-chloro-5-quinolinyl]-cyclohexaneacetamide

Product 1

HCID 11191005N-[2-[3-(Butylamino)propyl]-6-chloro-5-quinolinyl]-cyclohexaneacetamide dihydrochloride

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A solution of N-[2-(3-aminopropyl)-6-chloro-5-quinolinyl]-cyclohexaneacetamide (0.2 g) (Example 23), acetic acid (1 drop) and butanal (0.074 mL) in tetrahydrofuran was placed in a 10 mL vial and heated at 100° C. for 30 minutes within a microwave. Once the reaction had cooled to room temperature sodium triacetoxyborohydride (0.236 g) was added and the mixture stirred for 12 hours. The solvent was removed and the residue taken up in dimethylsulfoxide (3 mL). The residue was purified by HPLC (Waters Symmetry column using 25% to 95% acetonitrile in 0.1% aqueous trifluoroacetic acid). Further purification (SiO2, ammonia:methanol:dichloromethane, 1:4:95 as eluant) followed by removal of solvent and conversion to its hydrochloride salt with 4M hydrogen chloride in 1,4-dioxane (5 mL) afforded the title product (0.021 g).

Workup

  1. additionwas added
  2. customThe solvent was removed
  3. customThe residue was purified by HPLC (Waters Symmetry column using 25% to 95% acetonitrile in 0.1% aqueous trifluoroacetic acid)
  4. customFurther purification (SiO2, ammonia:methanol:dichloromethane, 1:4:95 as eluant)
  5. customfollowed by removal of solvent and conversion to its hydrochloride salt with 4M hydrogen chloride in 1,4-dioxane (5 mL)

Sources & evidence

ORD record
ord-776c2818cd984807af20728528224ea1
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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