1-Butanol → {[2-(6-Butoxy-pyridin-3-yl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carbonyl]-amino}-acetic acid methyl ester

HRID 642396Notes

Reaction equation

HRID 642396 reaction equation
C(O[C:4]([C:6]1[N:11]=[CH:10][C:9]2[N:12]=[C:13]([C:15]3[CH:16]=[N:17][C:18](Cl)=[CH:19][CH:20]=3)[S:14][C:8]=2[C:7]=1[OH:22])=[O:5])C.[CH3:23][CH2:24][CH2:25][CH2:26][O-:27].[Na+].C(O)CCC.Cl.CN(C)CCCN=C=NCC.Cl.[CH3:47][O:48][C:49](=[O:52])[CH2:50][NH2:51].Cl>CN(C)C1C=CN=CC=1.CN(C)C=O.C(Cl)(Cl)Cl>[CH3:47][O:48][C:49](=[O:52])[CH2:50][NH:51][C:4]([C:6]1[N:11]=[CH:10][C:9]2[N:12]=[C:13]([C:15]3[CH:16]=[N:17][C:18]([O:27][CH2:26][CH2:25][CH2:24][CH3:23])=[CH:19][CH:20]=3)[S:14][C:8]=2[C:7]=1[OH:22])=[O:5]

Participants

10

Reactant 6

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 122755Glycine methyl ester hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23669364Sodium n-butylateHCID 866173622-(6-Chloro-pyridin-3-yl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester

Product 1

HCID 68428062{[2-(6-Butoxy-pyridin-3-yl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carbonyl]-amino}-acetic acid methyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

2-(6-Chloro-pyridin-3-yl)-7-hydroxy-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester, example 92(c)(0.15 g, 0.45 mmol) was added to a solution of sodium 1-butoxide in 1-butanol (prepared by dissolving sodium (45.2 mg, 1.96 mmol) in 10 mL of anhydrous 1-butanol) at ambient temperature. After the reaction mixture was refluxed overnight, the solvent was evaporated off. The resulting residue was added to a suspension of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (94.3 mg, 0.49 mmol), glycine methyl ester hydrochloride (61.8 mg, 0.49 mmol), hydrochloric acid (10 N, 98.3 μL, 0.983 mmol), and 4-dimethylaminopyridine (5.46 mg, 0.045 mmol) in N,N-dimethylformamide at ambient temperature. The reaction mixture was stirred at ambient temperature overnight before 60 mL of chloroform was added. The organic solution was washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate solution, and brine, dried, filtered, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-100% ethyl acetate in hexanes to produce 10.6 mg of a white solid. MS: (+) m/z 417.3 (M+1).

Workup

  1. temperatureAfter the reaction mixture was refluxed overnight
  2. customthe solvent was evaporated off
  3. additionwas added
  4. washThe organic solution was washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate solution, and brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. washeluting from silica gel with a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a23acd0a0ca74b919272be4243b13ce2
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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