3-Hydroxypicolinic Acid → HCID 59513077, compound

HRID 1024527Notes

Reaction equation

HRID 1024527 reaction equation
[OH:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1.Cl.[C:42]([O:46][C:47](=[O:50])[CH2:48][NH2:49])([CH3:45])([CH3:44])[CH3:43]>CN(C=O)C>[C:42]([O:46][C:47](=[O:50])[CH2:48][NH:49][C:8]([C:3]1[C:2]([OH:1])=[CH:7][CH:6]=[CH:5][N:4]=1)=[O:10])([CH3:45])([CH3:44])[CH3:43]

Participants

7

Reactant 5

HCID 134013-Hydroxypicolinic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2725036Glycine tert-butyl ester hydrochloride

Product 1

HCID 59513077HCID 59513077, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-hydroxypicolinic acid (0.20 g, 1.44 mmol) in DMF (5 mL) at 0° C. under N2 is added diisopropylethylamine (DIPEA) (0.75 ml, 4.3 mmol), 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide (EDCI) (0.412 g, 2.9 mmol) and 1-hydroxybenzo-triazole (HOBt) (0.019 g, 0.14 mmol). The resulting mixture is stirred for 5 min before glycine tert-butyl ester HCl (0.36 g, 2.9 mmol) is introduced. The resulting solution is stirred at room temperature for 3 days then concentrated under reduced pressure. The reaction mixture is diluted with EtOAc then washed with 1M HCl, sat. NaCl, and the organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to a crude oil that is purified over silica (EtOAc/heptane 1:4) to afford 0.078 g (22% yield) of the desired compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.80 (1H, s), 8.39 (1H, br s), 8.02 (1H, dd, J=4.4, 1.5 Hz), 7.27 (1H, dd, J=8.8, 4.4 Hz), 7.25 (1H, dd, J=8.4, 1.5 Hz), 4.06 (2H, d, J=5.5 Hz), 1.44 (9H, s). HPLC-MS: m/z 197 [M-tBu]+.

Workup

  1. additionis introduced
  2. concentrationthen concentrated under reduced pressure
  3. additionThe reaction mixture is diluted with EtOAc
  4. washthen washed with 1M HCl, sat. NaCl
  5. dry with materialthe organic layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a crude oil that
  8. customis purified over silica (EtOAc/heptane 1:4)

Sources & evidence

ORD record
ord-0a66553310cf46efb0579a6ed759425b
Source dataset
uspto-grants-2014_05
Patent number
US08722895B2

Reaction notes

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