Methanamine, N-methoxy-, hydrochloride (1:1) → Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 906074Notes

Reaction equation

HRID 906074 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN([C:26]([O:30][N:31]1N=NC2C=CC=N[C:32]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.CNOC>CN(C=O)C>[CH3:26][O:30][N:31]([CH3:32])[C:18]([C:17]1[CH:21]=[CH:22][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[N:15][CH:16]=1)=[O:19]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27718236-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 86631940Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylateYield 63.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)nicotinic acid (2.0 g, 6.5 mmol) was taken into DMF (10 mL) followed by addition of HATU (2.48 g, 6.5 mmol), N,N-diisopropylethylamine (2.5 mL, 14.1 mmol) and N,O-dimethylhydroxylamine hydrochloride (652 mg, 6.7 mmol), and the mixture was stirred at room temperature over 12 hours. The resulting solution was partitioned with ethyl acetate and water then the organic phase washed with water (3×), 10% aqueous citric acid (2×) then 0.5M aqueous sodium hydroxide and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated, then purified by silica gel flash chromatography with ethyl ether as eluent to provide tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate (1.45 g). MS (EI) for C17H26N4O4: 351 (MH+).

Workup

  1. customThe resulting solution was partitioned with ethyl acetate and water
  2. washthe organic phase washed with water (3×), 10% aqueous citric acid (2×)
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel flash chromatography with ethyl ether as eluent

Sources & evidence

ORD record
ord-6804a1280c1a484da5c92b6af64ccca4
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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