Hydrochloric Acid → 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid

HRID 1518271Notes

Reaction equation

HRID 1518271 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[S:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[NH:19][C:20]([C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[CH2:30][N:29]([C:32]1[S:33][C:34]([CH2:42][CH2:43][CH2:44]I)=[C:35]([C:37]([O:39]CC)=[O:38])[N:36]=1)[CH2:28][CH2:27]2)=[O:21].Cl.[OH-].[Na+]>CN(C=O)C>[S:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]=[C:11]1[NH:19][C:20]([C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:31]=1[CH2:30][N:29]([C:32]1[S:33][C:34]([CH2:42][CH2:43][CH2:44][O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:35]([C:37]([OH:39])=[O:38])[N:36]=1)[CH2:28][CH2:27]2)=[O:21]

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 996PhenolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylate

Product 1

HCID 468365682-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid (2) was prepared by the following procedure: To phenol (22.6 mg, 0.24 mmol) in DMF (2 mL) was added NaH (60% oil dispersion) (24 mg, 0.6 mmol). After stirring at rt for 5 minutes, ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylate (2C) (127 mg, 0.2 mmol) was added and stirring was continued for 1 hour. The reaction mixture was acidified with 1N HCl and the precipitate was filtered and washed with water. The precipitate was slurried in Et2O, filtered and washed with additional Et2O. The resulting solid was purified by column chromatography on silica gel eluting with a gradient of 0 to 2% MeOH in DCM. To the purified material in DMF (1 mL) was added NaOH (4N aq) (0.5 mL, 2 mmol), heated at 50° C. for 5 hours, cooled to rt, and acidified with 1N HCl. The precipitate was filtered, washed with water, slurried in Et2O, filtered, washed with Et2O and dried in a vacuum oven to provide the desired product 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid (2) in 37% yield. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.89 (s, 1H), 12.49 (1H, s), 8.04 (1H, d), 7.79 (1H, d), 7.67 (1H, d), 7.44 (4H, m), 7.25 (2H, m), 6.88 (3H, m), 4.82 (2H, s), 3.96 (2H, t), 3.72 (2H, t), 3.17 (2H, m), 3.03 (2H, t), 2.00 (2H, m). MS (ESI(+)): m/z 571 (M+H).

Workup

  1. customThe title compound 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid (2) was prepared by the following procedure
  2. stirringstirring
  3. waitwas continued for 1 hour
  4. filtrationthe precipitate was filtered
  5. washwashed with water
  6. filtrationfiltered
  7. washwashed with additional Et2O
  8. customThe resulting solid was purified by column chromatography on silica gel eluting with a gradient of 0 to 2% MeOH in DCM
  9. temperatureheated at 50° C. for 5 hours
  10. temperaturecooled to rt
  11. filtrationThe precipitate was filtered
  12. washwashed with water
  13. filtrationfiltered
  14. washwashed with Et2O
  15. customdried in a vacuum oven

Sources & evidence

ORD record
ord-8fac068ec44c40daacf7ab94b1ec6c00
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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