Hydrochloric Acid → HCID 69473945, compound

HRID 990922Notes

Reaction equation

HRID 990922 reaction equation
[C:1](NC1C=CC=CC=1)(=O)[CH3:2].[S:11](=[O:15])(=O)(O)O.[NH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]1=O.C(I)(C)C.[F-].[Cs+].Cl.[NH2:34]CCS.[H-].[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].C=O.N=O.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]3[NH:34][S:11](=[O:15])[CH:2]=[CH:1][C:24]3=2)[CH:19]=[CH:18][CH:17]=1

Participants

14

Reactant 12

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 904AcetanilideHCID 945NitroxylHCID 1118Sulfuric AcidHCID 60382-HydroxyquinolineHCID 6362Isopropyl iodideHCID 9082Cysteamine HydrochlorideHCID 24758Sodium hydrideHCID 25953Cesium fluorideHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 69473945HCID 69473945, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Thiazino-quinolinone compounds (e.g., Structure 56) are prepared as shown in Scheme XI. The process of Scheme XI begins with the treatment of an aniline, for example, 4-bromo-3-chloroaniline, with a β-ketoester or its corresponding hydrate, for example 4,4,4-trifluoroacetoacetate, at elevated temperatures, to afford the corresponding acetanilide. Treatment of the acetanilide with an acid, for example, sulfuric acid, affords the corresponding 1H-quinolin-2-one (an example of a Knorr cyclization as described further herein). Protection of the pyridone ring, with, for example, isopropyl iodide, mediated by a base, for example, cesium fluoride, affords a compound of Structure 51. Treatment of a compound (e.g., Structure 51) with a β-aminothiol, for example, 2-aminoethanethiol hydrochloride, mediated by a base, for example, sodium hydride, affords a compound of Structure 52. Treatment of a compound of Structure 52 with a ligated transition metal. for example palladium acetate and BINAP, in the presence of a base, for example sodium t-butoxide, at elevated temperatures, affords a compound of Structure 53, See S. Wagaw, et al., J. Am. Chem. Soc. 1997, 119, 8451-8458. Treatment of a compound of Structure 53 with an aldehyde or its corresponding hydrate or hemiacetal, for example, formaldehyde, affords a compound of Structure 55. Hydrolysis of the imino ether can be accomplished by treatment of a compound of Structure 55 with an acid, for example hydrochloric acid, at elevated temperatures, to afford a thiazino-quinolinone compound such as Structure 56. Alternatively, a compound of Structure 53 can be deprotected with an acid, for example hydrochloric acid, at elevated temperatures, to afford a thiazino-quinolinone compound such as Structure 54.

Workup

  1. customaffords a compound of Structure 51
  2. customaffords a compound of Structure 52

Sources & evidence

ORD record
ord-620c48e676e84d6ab34edbfb7bc88795
Source dataset
uspto-grants-2002_10
Patent number
US06462038B1

Reaction notes

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