Acetic Acid → N-(1-Adamantylmethyl)-5-chloro-2-({[3-(methylamino)propyl]amino}methyl)isonicotinamide dihydrochloride

HRID 1247608Notes

Reaction equation

HRID 1247608 reaction equation
[C:1]12([CH2:11][NH:12][C:13](=[O:23])[C:14]3[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([CH:21]=O)[CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH2:24][CH2:25][CH2:26][CH2:27][N:28](C)[C:29](=O)OC(C)(C)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[ClH:20].[ClH:20].[C:1]12([CH2:11][NH:12][C:13](=[O:23])[C:14]3[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([CH2:21][NH:24][CH2:25][CH2:26][CH2:27][NH:28][CH3:29])[CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2756543tert-butyl N-(3-aminopropyl)-N-methylcarbamateHCID 5049666Sodium triacetoxyborohydrideHCID 21906741N-(1-Adamantylmethyl)-5-chloro-2-formylisonicotinamide

Product 1

HCID 21906671N-(1-Adamantylmethyl)-5-chloro-2-({[3-(methylamino)propyl]amino}methyl)isonicotinamide dihydrochlorideYield 114.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

N-(1-Adamantylmethyl)-5-chloro-2-formylisonicotinamide (Example 29(ii)) (0.2 g) was dissolved in methanol (10 mL) and tert-butyl 3-aminopropyl(methyl)carbamate, (0.39 g) added along with acetic acid (0.2 mL). The mixture was stirred for 15 minutes at ambient temperature and then sodium triacetoxyborohydride (0.25 g) was added and the reaction stirred for 20 hours, concentrated and the residue partitioned between 2M aqueous hydrochloric acid solution (10 mL) and ethyl acetate (10 mL). The layers were separated and the organic phase re-extracted with 2N hydrochloric acid (2×10 mL). The combined aqueous extracts were basified with 5M aqueous ammonium hydroxide solution, extracted into ethyl acetate (2×25 mL) and the combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was dissolved in dichloromethane and treated with dry hydrogen chloride in 1,4-dioxane (4N, 1 mL) and was concentrated after 2 hours to give the deprotected material. The residue was recrystallised from dichloromethane (10 mL) to afford the titled compound (0.110 g).

Workup

  1. stirringthe reaction stirred for 20 hours
  2. concentrationconcentrated
  3. customthe residue partitioned between 2M aqueous hydrochloric acid solution (10 mL) and ethyl acetate (10 mL)
  4. customThe layers were separated
  5. extractionthe organic phase re-extracted with 2N hydrochloric acid (2×10 mL)
  6. extractionextracted into ethyl acetate (2×25 mL)
  7. dry with materialthe combined extracts were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in dichloromethane
  11. additiontreated with dry hydrogen chloride in 1,4-dioxane (4N, 1 mL)
  12. concentrationwas concentrated after 2 hours
  13. customto give the deprotected material
  14. customThe residue was recrystallised from dichloromethane (10 mL)

Sources & evidence

ORD record
ord-7d5a8115836844fbb9fed0350a1da9df
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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