6-Aminonicotinic acid → HCID 58869827, compound

HRID 2402283Notes

Reaction equation

HRID 2402283 reaction equation
[CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH2:18][CH2:19][C:20](NC1SC=CN=1)=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:34][C:35]1[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][N:36]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.Cl>[CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[CH2:18][CH2:19][C:20]([NH:34][C:35]1[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][N:36]=1)=[O:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 184966-Aminonicotinic acidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 58869823HCID 58869823, compound

Product 1

HCID 58869827HCID 58869827, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The product from Example 1, Part E (300 mg, 1.02 mmol) was taken up in 4 mL CH2Cl2 and cooled to 0° C. Oxalyl chloride (0.1 mL, 1.22 mmol) was added slowly and stirring continued for 0.5 h. A slurry of 6-aminonicotinic acid (211 mg, 1.53 mmol) and diisopropylethylamine (0.27 mL, 1.53 mmol) was added slowly and stirring continued at room temperature for 16 h. Three drops of conc. HCl was added and the organic phase was washed with brine. The organic phase was dried (Na2SO4), filtered and evaporated. The product was purified by silica gel chromatography (12 mg, 3%). 1H NMR (400 MHz, CDCl3) δ 10.69 (s, 1H), 8.70 (m, 1H), 8.32 (m, 1H), 7.87 (m, 1H), 7.52 (m, 3H), 7.34 (m, 6H), 5.46 (m, 1H), 4.60 (br s, 1H), 4.31 (m, 1H), 2.54 (m, 2H), 2.09 (m, 2H). MS: m/z (MH+) 416.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 16 h
  3. washthe organic phase was washed with brine
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe product was purified by silica gel chromatography (12 mg, 3%)

Sources & evidence

ORD record
ord-66cb4afc0ccb493e8f1441d76ce581d5
Source dataset
uspto-grants-2014_08
Patent number
US08796313B2

Reaction notes

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