Dimethylformamide → 3-Amino-N-methylpicolinamide

HRID 1948041Notes

Reaction equation

HRID 1948041 reaction equation
[NH2:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:11][N:12](C=O)C.CCN(C(C)C)C(C)C.Cl.CN.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O>[NH2:1][C:2]1[C:3]([C:8]([NH:12][CH3:11])=[O:10])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 738363-Aminopicolinic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochloride

Product 1

HCID 135332483-Amino-N-methylpicolinamideYield 35.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 3-aminopicolinic acid (0.3 g, 2 mmol) in DMF (2.0 mL, 26 mmol) was cooled to 0° C., treated with DIPEA (7.57 mL, 43.4 mmol), methylamine hydrochloride (1.47 g, 21.7 mmol) and TBTU (0.837 g, 2.61 mmol). The flask was sealed and the mixture was allowed to come up to RT stirring for 3 hours. The reaction mixture was poured into water and extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, filtered and concentrated to an oil which was passed through an ion exchange column (SCX). The MeOH/NH3 washes were combined to isolate 108 mg of a brown oil which crystallized upon standing. 1H NMR (400 MHz, DMSO-d6) d 2.76 (d, J=4.80 Hz, 3H), 6.81 (br. s., 2H), 7.13 (dd, J=8.30, 1.50 Hz, 1H), 7.22 (dd, J=8.30, 4.30 Hz, 1H), 7.77 (dd, J=4.17, 1.39 Hz, 1H), 8.52 (d, J=3.79 Hz, 1H). MS (ES+): m/z=152.04 [MH+].

Workup

  1. customThe flask was sealed
  2. customto come up to RT
  3. extractionextracted with EtOAc three times
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to an oil which

Sources & evidence

ORD record
ord-5465220088334e3a824ce47a3e05364a
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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