Amantadine → N-adamantan-1-yl-2,6-dichloronicotinamide

HRID 1187375Notes

Reaction equation

HRID 1187375 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2.C(N(C(C)C)C(C)C)C>C(Cl)Cl.CCOC(C)=O>[C:13]12([NH:12][C:4](=[O:5])[C:3]3[CH:7]=[CH:8][C:9]([Cl:11])=[N:10][C:2]=3[Cl:1])[CH2:20][CH:19]3[CH2:18][CH:17]([CH2:16][CH:15]([CH2:21]3)[CH2:14]1)[CH2:22]2

Participants

6

Reactant 3

HCID 2130AmantadineHCID 81531DiisopropylethylamineHCID 122639842,6-Dichlorpyridine-3-carbonyl chloride

Product 1

HCID 59830746N-adamantan-1-yl-2,6-dichloronicotinamideYield 85.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2,6-dichloronicotinoyl chloride (4.21 g, 20 mmol) in DCM (20 mL) was added dropwise to a stirred suspension of 1-aminoadamantane (3.03 g, 20 mmol) and N-ethyldiisopropylamine (4.19 mL, 24 mmol) in DCM (20 mL) at 0° C., over a period of 30 minutes under nitrogen. The resulting suspension was stirred at room temperature for 18 hours. The reaction mixture was diluted with EtOAc (500 mL), and washed sequentially with water (100 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% Et2O in DCM. Pure fractions were evaporated to dryness to afford N-adamantan-1-yl-2,6-dichloronicotinamide (5.57 g, 76%) as a white solid.

Workup

  1. washwashed sequentially with water (100 mL) and saturated brine (50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% Et2O in DCM
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b447cf0433dd417692e48c4a285c2727
Source dataset
uspto-grants-2014_03
Patent number
US08673938B2

Reaction notes

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