Hydrochloric Acid → Methyl 2-[8-[(2-benzothiazolylamino)carbonyl]-3,4-dihydro-2(1H)-isoquinolinyl]-5-iodo-4-thiazolecarboxylate

HRID 1518275Notes

Reaction equation

HRID 1518275 reaction equation
Cl.Cl.[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[NH:12][C:13]([C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:24]=1[CH2:23][NH:22][CH2:21][CH2:20]2)=[O:14].Cl[C:26]1[S:27][C:28]([I:35])=[C:29]([C:31]([O:33][CH3:34])=[O:32])[N:30]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>CC(N(C)C)=O>[S:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[NH:12][C:13]([C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:24]=1[CH2:23][N:22]([C:26]1[S:27][C:28]([I:35])=[C:29]([C:31]([O:33][CH3:34])=[O:32])[N:30]=1)[CH2:21][CH2:20]2)=[O:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 59447499Methyl 2-chloro-5-iodo-1,3-thiazole-4-carboxylateHCID 86644320N-(benzo[d]thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline-8-carboxamide dihydrochloride

Product 1

HCID 59447550Methyl 2-[8-[(2-benzothiazolylamino)carbonyl]-3,4-dihydro-2(1H)-isoquinolinyl]-5-iodo-4-thiazolecarboxylateYield 66.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-(benzo[d]thiazol-2-yl)-1,2,3,4-tetrahydroisoquinoline-8-carboxamide dihydrochloride (1B) (2 g, 5.23 mmol) and methyl 2-chloro-5-iodothiazole-4-carboxylate (8B) (1.66 g, 5.23 mmol) in DMA (10 mL) was added Cs2CO3 (8.52 g, 26.2 mmol). The reaction mixture was stirred at 60° C. overnight, cooled to rt, acidified with 5% HCl, extracted with DCM, washed with water, brine, dried over Na2SO4, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel and eluted with 5% MeOH in DCM to provide 2.0 g (65%) of the desired product 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-iodothiazole-4-carboxylate (8C): LC/MS (APCI): m/z 577.0 (M+H)

Workup

  1. temperaturecooled to rt
  2. extractionextracted with DCM
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by column chromatography on silica gel
  7. washeluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-7268b8d81e96411ca7fdf4a4c96168d1
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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