Dimethylformamide → 5-(1-Phenylcyclopropyl)-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiazolo[5,4-b]pyridine

HRID 1177586Notes

Reaction equation

HRID 1177586 reaction equation
CN(C=O)C.C(OC([N:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:23](O)=O)[CH:19]=2)[CH2:14]1)=O)(C)(C)C.C(Cl)(=O)C(Cl)=O.[NH2:32][C:33]1[C:34](=[S:48])[NH:35][C:36]([C:39]2([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:41][CH2:40]2)=[CH:37][CH:38]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(Cl)Cl.C1(C)C=CC=CC=1>[C:42]1([C:39]2([C:36]3[N:35]=[C:34]4[S:48][C:23]([C:18]5[CH:19]=[C:20]6[C:15](=[CH:16][CH:17]=5)[CH2:14][NH:13][CH2:22][CH2:21]6)=[N:32][C:33]4=[CH:38][CH:37]=3)[CH2:40][CH2:41]2)[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 65578Oxalyl chlorideHCID 113578872-(tert-Butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acidHCID 591748363-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione

Product 1

HCID 591748385-(1-Phenylcyclopropyl)-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

DMF (27.8 μL, 0.358 mmol) was added to a solution of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (198.6 mg, 0.716 mmol) and oxalyl chloride (66 μL, 0.757 mmol) in DCM (7.0 mL), and the resulting mixture was stirred at 25° C. for 4 h. The reaction mixture was then concentrated in vacuo and 3-amino-6-(1-phenylcyclopropyl)pyridine-2(1H)-thione (175 mg, 0.720 mmol) was added. The resulting mixture was taken up in toluene (7.0 mL) and stirred at 25° C. for 5 min then at 100° C. for 1.5 h. (±)-10-camphorsulfonic acid (184 mg, 0.792 mmol) was then added, and the resulting mixture was heated at 100° C. for 1.5 h. The reaction mixture was subsequently cooled to 25° C. and purified by column chromatography (silica gel, 0-10% MeOH/DCM) to provide crude product, which was taken up in DCM (100 mL) and sequentially washed with sat. aq. NaHCO3 and brine. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 5-(1-phenylcyclopropyl)-2-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiazolo[5,4-b]pyridine as a light yellow solid. MS (ESI) m/z: Calculated: 383.1; Observed: 384.1 (M++1).

Workup

  1. additionwas added
  2. stirringstirred at 25° C. for 5 min
  3. temperaturethe resulting mixture was heated at 100° C. for 1.5 h
  4. temperatureThe reaction mixture was subsequently cooled to 25° C.
  5. custompurified by column chromatography (silica gel, 0-10% MeOH/DCM)
  6. customto provide crude product, which
  7. washsequentially washed with sat. aq. NaHCO3 and brine
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9d4c7d8346324c378c995ac010fed848
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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