N,N-Dimethylpropargylamine → 3-[5-(7-azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amine

HRID 1908223Notes

Reaction equation

HRID 1908223 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:11]2[CH:15]3[CH2:16][CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH3:18][N:19]([CH3:23])[CH2:20][C:21]#[CH:22]>CN(C=O)C.C(N(CC)CC)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:15]12[N:11]([C:4]3[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([C:22]#[C:21][CH2:20][N:19]([CH3:23])[CH3:18])[CH:3]=3)[CH:12]([CH2:17][CH2:16]1)[CH2:13][CH2:14]2

Participants

7

Reactant 2

HCID 81643N,N-DimethylpropargylamineHCID 575168467-(3-Bromo-4-nitrophenyl)-7-azabicyclo[2.2.1]heptane

Product 1

HCID 584786333-[5-(7-azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amineYield 79.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 7-(3-bromo-4-nitro-phenyl)-7-azabicyclo[2.2.1]heptane 25 (500 mg, 1.683 mmol), Pd(PPh3)2Cl2 (59 mg, 0.08 mmol), and cuprous iodide (9.616 mg, 1.708 μL, 0.05049 mmol) was added a solution of N,N-dimethylprop-2-yn-1-amine (420 mg, 538 μL, 5.05 mmol) in degassed DMF (5 mL) and triethylamine (5 mL). The reaction mixture was microwaved under N2 for 10 min at 100° C. The reaction was diluted with ethyl acetate, washed with 50% saturated sodium bicarbonate solution (2×20 mL), water, and brine. The solution was dried over anhydrous Na2SO4 and filtered, leaving a red solid. Purification by silica gel chromatography (0-50% dichloromethane in ethyl acetate) yielded 3-[5-(7-azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amine 26 (400 mg, 79% yield). LC/MS m/z 300.5 [M+H]+, retention time 1.11 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min).

Workup

  1. customThe reaction mixture was microwaved under N2 for 10 min at 100° C
  2. washwashed with 50% saturated sodium bicarbonate solution (2×20 mL), water, and brine
  3. dry with materialThe solution was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customleaving a red solid
  6. customPurification by silica gel chromatography (0-50% dichloromethane in ethyl acetate)

Sources & evidence

ORD record
ord-0c26bc8db85c4bababd56bf3a3ca6fa0
Source dataset
uspto-grants-2013_12
Patent number
US08598205B2

Reaction notes

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