Triethylamine → Methyl 3-nitro-5-(thiazolo[5,4-c]pyridin-2-yl)benzoate

HRID 416596

Reaction equation

HRID 416596 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:14]([O-])=O)[CH:7]=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.C(N(C(C)C)C([S:29][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:35]=1[NH2:36])=S)(C)C.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[N+:1]([C:4]1[CH:13]=[C:8]([CH:7]=[C:6]([C:14]2[S:29][C:30]3[CH:31]=[N:32][CH:33]=[CH:34][C:35]=3[N:36]=2)[CH:5]=1)[C:9]([O:11][CH3:12])=[O:10])([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 6931682Monomethyl-5-nitroisophthalateHCID 11437145Carbamodithioic acid, bis(1-methylethyl)-, 4-amino-3-pyridinyl ester

Product 1

HCID 59679842Methyl 3-nitro-5-(thiazolo[5,4-c]pyridin-2-yl)benzoateYield 56.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Mono-methyl 5-nitro-isophthlate (1.25 g, 5.58 mmol) was suspended in 25 mL of CH2Cl2 and oxalyl chloride (0.49 mL, 5.58 mmol) was added. After 3 drops of DMF was added, the reaction mixture was stirred at room temperature until all gas evolution had ceased and all the solids had dissolved. This freshly prepared solution of the acid chloride was then added dropwise to a solution of 4-aminopyridin-3-yl diisopropylcarbamodithioate (1.5 g, 5.58 mmol) and triethylamine (0.77 mL, 5.58 mmol) in 50 mL of CH2Cl2 at 0° C. The resulting reaction mixture was warmed to room temperature and stirred for 1 hour. It was then quenched with 25 mL of brine and the two layers were separated. The organic layer was dried (Na2SO4) and concentrated. The resulting residue was suspended in 25 mL of 2 N HCl and stirred under reflux for 30 min. It was then cooled to room temperature and the solids were collected by filtration and dried to afford 1.0 g of methyl 3-nitro-5-(thiazolo[5,4-c]pyridin-2-yl)benzoate. This material was then mixed with 20 mL of methanol and 3 mL of water along with 1 g of sodium hydrosulfide hydrate and stirred under reflux for 2 hours. The resulting reaction mixture was cooled and concentrated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4) and concentrated to afford 150 mg of methyl 3-amino-5-(thiazolo[5,4-c]pyridin-2-yl)benzoate (MS, M++H=286).

Workup

  1. dissolutionall the solids had dissolved
  2. customThe resulting reaction mixture
  3. temperaturewas warmed to room temperature
  4. stirringstirred for 1 hour
  5. customIt was then quenched with 25 mL of brine
  6. customthe two layers were separated
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated
  9. stirringstirred
  10. temperatureunder reflux for 30 min
  11. temperatureIt was then cooled to room temperature
  12. filtrationthe solids were collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-e318314c47cb4bc897d26934c8af9dca
Source dataset
uspto-grants-2012_01
Patent number
US08088928B2

Linked notes

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