Diisopropylethylamine → 2-Methylnicotinamide

HRID 1919838Notes

Reaction equation

HRID 1919838 reaction equation
[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C[N:12](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:12])=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6433732-Methylnicotinic 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 122437052-MethylnicotinamideYield 76.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-methylnicotinic acid (0.537 mg, 3.9 mmol) in 20 mL of DMF at 0° C. was added HATU (1.56 g, 4.1 mmol) followed by the dropwise addition of DIPEA (0.72 ml, 4.1 mmol). NH3 (g) was then bubbled into the solution for 15 mins. The reaction was allowed to stir overnight. The resulting paste was filtered and rinsed with cold DMF and discarded. The mother liquor was concentrated and purified by normal phase chromatography using CH2Cl2/7 N NH3 in MeOH: 93/7 as eluent. Yielded a white solid (405 mg, 76%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.34 (s, 9 H), 1.36 (d, J=6.64 Hz, 3H), 2.56 (s, 3 H), 4.32-4.40 (m, 1 H), 7.15-7.19 (m, J=8.20 Hz, 1 H), 7.68 (d, J=8.20 Hz, 1 H)

Workup

  1. customNH3 (g) was then bubbled into the solution for 15 mins
  2. filtrationThe resulting paste was filtered
  3. washrinsed with cold DMF
  4. concentrationThe mother liquor was concentrated
  5. custompurified by normal phase chromatography

Sources & evidence

ORD record
ord-c3e52665ba194571b475008742c4ef25
Source dataset
uspto-grants-2012_05
Patent number
US08168668B2

Reaction notes

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