Hydrochloric Acid → 2-(8-(Benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid

HRID 1518279Notes

Reaction equation

HRID 1518279 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([CH2:32][CH2:33][CH2:34][O:35]S(C3C=CC(C)=CC=3)(=O)=O)=[C:26](C(OC)=O)[N:27]=1)[CH2:19][CH2:18]2)=[O:12].O[C:47]1[CH:56]=[CH:55][CH:54]=[C:53]2[C:48]=1[CH:49]=[CH:50][N:51]=[CH:52]2.[C:57]([O-:60])([O-])=[O:58].[Cs+].[Cs+].Cl>CC(N(C)C)=O.[OH-].[Na+]>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([CH2:32][CH2:33][CH2:34][O:35][C:56]3[CH:47]=[C:48]4[C:53](=[CH:54][CH:55]=3)[CH:52]=[N:51][CH:50]=[CH:49]4)=[C:26]([C:57]([OH:60])=[O:58])[N:27]=1)[CH2:19][CH2:18]2)=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 30386Isoquinolin-5-olHCID 59447681methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(tosyloxy)propyl)thiazole-4-carboxylate

Product 1

HCID 594475082-(8-(Benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 31374DimethylacetamideSolvent

Procedure

The title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8) was prepared by the following procedure: To a solution of methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(tosyloxy)propyl)thiazole-4-carboxylate (8F) (133 mg, 0.2 mmol) and 5-hydroxyisoquinoline (45 mg, 0.3 mmol) in DMA (3 mL) was added Cs2CO3 (50 mg, 0.3 mmol). The mixture was stirred at rt overnight and was diluted with 2N NaOH (4 mL) and stirred at 50° C. for 4 hours. The reaction mixture was neutralized with 5% HCl and the precipitate was filtered and dried. The residue was then dissolved in DMSO/MeOH (1:1) and purified by column chromatography on silica gel to provide the desired product 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8): 1H NMR (300 MHz, DMSO-D6) δ ppm 9.16 (1H, s), 8.34 (1H, d), 7.94 (1H, d), 7.85 (1H, d), 7.71 (4H, m), 7.38 (8H, m), 4.88 (2H, s), 4.14 (2H, t), 3.71 (2H, t), 3.00 (2H, t), 2.27 (1H, m), 2.09 (2H, m). LC/MS (APCI): m/z 622.2 (M+H).

Workup

  1. customThe title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(isoquinolin-6-yloxy)propyl)thiazole-4-carboxylic acid (8) was prepared by the following procedure
  2. stirringstirred at 50° C. for 4 hours
  3. filtrationthe precipitate was filtered
  4. customdried
  5. dissolutionThe residue was then dissolved in DMSO/MeOH (1:1)
  6. custompurified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c82868997fbd482dace3c3402d2e0dd1
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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