Dimethylformamide → HCID 59200361, compound

HRID 1685334Notes

Reaction equation

HRID 1685334 reaction equation
CN(C=O)C.Cl[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([C:13]([OH:15])=[O:14])[CH:8]=1.O.[SH2:17].[Na].C[O-].[Na+].Br[C:23]1[S:27][C:26]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[N:25][CH:24]=1>CO>[N:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[NH:28][C:26]1[S:27][C:23]([S:17][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([OH:15])=[O:14])[CH:8]=2)=[CH:24][N:25]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 2308904-Chloropyridine-2-carboxylic acidHCID 53294005-bromo-N-(pyridin-2-yl)thiazol-2-amineHCID 10942334Sodium MethoxideHCID 53442613Sodium hydrogen sulfide hydrate

Product 1

HCID 59200361HCID 59200361, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A DMF (3 mL) suspension of 4-chloropicolinic acid (0.160 g, 1.01 mmol) and sodium hydrogensulfide hydrate (0.225 g, 3.03 mmol, 3 eq) was heated to 100° C. After 3 h, the suspension was diluted with methanol (10 mL), 5-bromo-N-(pyridine-2-yl)thiazol-2-amine (0.256 g, 1.0 mmol, 1 eq, described in the synthesis of thiazoles Example A) was added followed by a solution of sodium methoxide 25% (2 mL). The resulting mixture was heated at 80° C. for 15 min., concentrated to remove most of the methanol, diluted with DMF and acidified with acetic acid. The resulting solution was purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound as a solid (0.094 mg, 28%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.00 (1H, dd, J=6.69, 5.68 Hz), 7.12 (1H, d, J=8.34 Hz), 7.34 (1H, dd, J=5.31, 1.77 Hz), 7.68 (1H, d, J=1.52 Hz), 7.73-7.83 (2H, m), 8.31 (1H, d, J=4.04 Hz), 8.48 (1H, d, J=5.31 Hz), 11.80 (1H, s). LC/MS (M+H)+: 331, (M−H)−: 329.

Workup

  1. additionwas added
  2. temperatureThe resulting mixture was heated at 80° C. for 15 min.
  3. concentrationconcentrated
  4. customto remove most of the methanol
  5. additiondiluted with DMF
  6. customThe resulting solution was purified on preparative HPLC (ammonium acetate/water/acetonitrile)
  7. customfreeze dried

Sources & evidence

ORD record
ord-7a3da60903d94d6ca0724792ec2c58b1
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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