Hydrochloric Acid → HCID 59200394, compound

HRID 1685339Notes

Reaction equation

HRID 1685339 reaction equation
[SH:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([O:10]C)=[O:9])[CH:3]=1.O.S.[Na].Br[C:16]1[S:20][C:19]([NH:21][C:22]2[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][N:23]=2)=[N:18][CH:17]=1.SC1C=CC=CN=1.C[O-].[Na+].[OH-].[Na+].Cl>CO.O.CN(C=O)C>[CH3:28][C:26]1[CH:25]=[CH:24][N:23]=[C:22]([NH:21][C:19]2[S:20][C:16]([S:1][C:2]3[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=[O:9])[CH:3]=3)=[CH:17][N:18]=2)[CH:27]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10942334Sodium MethoxideHCID 53442613Sodium hydrogen sulfide hydrateHCID 59200337HCID 59200337, compoundHCID 178418616HCID 178418616, compoundHCID 178498628HCID 178498628, compound

Product 1

HCID 59200394HCID 59200394, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
35 °C

Procedure

A DMF (8 mL) suspension of methyl 4-mercaptopicolinate (1.40 g, 8.16 mmol, prepared as described in Org. Prep. and Proc. Int. vol. 29 no 1, p. 117 (1997)) and sodium hydrogensulfide hydrate (0.685 g, 12.24 mmol, 1.5 eq) was bubbled with argon and heated to 35° C. 5-bromo-N-(4-methylpyridin-2-yl)thiazol-2-amine (1.103 g, 4.08 mmol, 1 eq, described in the synthesis of bromides, Example A) was diluted in methanol (15 mL) and this was treated by the DMF suspension of mercaptopyridine followed by a solution of sodium methoxide (4.6M in methanol, 2.7 mL, 12.24 mmol). The reaction was purged with argon and stirred at 65° C. for 1 hour. The reaction was then concentrated to remove most of the methanol, diluted in ethyl acetate/THF and acidified with 1N HCl. The aqueous phase was extracted with ethyl acetate (3×) but part of the compound remained in the aqueous phase. The two phases were combined and evaporated. The residue was then mixed with aqueous sodium hydroxide (5N, 8 mL, 40.8 mmol) and methanol followed by water were added. The reaction was stirred at 23° C. overnight, then acidified with 1N HCl. Methanol was evaporated and the solid was collected by filtration to give the crude title material (0.812 g, 58%) as a solid which was used as such in the next reaction. LC/MS (M+H)+: 345. HPLC ret. time (Condition B): 1.187 min.

Workup

  1. customprepared
  2. customThe reaction was purged with argon
  3. concentrationThe reaction was then concentrated
  4. customto remove most of the methanol
  5. additiondiluted in ethyl acetate/THF
  6. extractionThe aqueous phase was extracted with ethyl acetate (3×) but part of the compound
  7. customevaporated
  8. additionwere added
  9. stirringThe reaction was stirred at 23° C. overnight
  10. customMethanol was evaporated
  11. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-a3563568bfb34c3192ae31569e95d29d
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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