1,2,3,4-Tetrahydroisoquinoline → 2-(1-Acetyl-6-fluoro-1H-indazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinoline

HRID 1377512Notes

Reaction equation

HRID 1377512 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:13])[CH:11]=2)[C:6]([CH2:14]Br)=[N:5]1)(=[O:3])[CH3:2].[CH2:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18][NH:17]1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:13])[CH:11]=2)[C:6]([CH2:14][N:17]2[CH2:18][CH2:19][C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16]2)=[N:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 228766611-Acetyl-3-bromomethyl-6-fluoro-1H-indazole

Product 1

HCID 540526552-(1-Acetyl-6-fluoro-1H-indazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinolineYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1-Acetyl-3-bromomethyl-6-fluoro-1H-indazole (0.53 g, 1.96 mmol) in CH2Cl2 (10 mL) was treated with 1,2,3,4-tetrahydroisoquinoline (0.261 g, 1.96 mmol) and Hunig's base (0.44 mL, 2.5 mmol) and the mixture stirred at 20° C. for 16 h. The mixture was poured into saturated aqueous sodium bicarbonate solution (25 mL) and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were dried (MgSO4), concentrated and the residue purified by flash chromatography (7%→12% EtOAc in hexane) to give the title compound as a white solid (475 mg, 53%); mp 106°-107° C. (from Et2O/hexane); 1H NMR (360 MHz, d6 -DMSO) δ 8.08 (dd, J=8.8, 5.4 Hz, 1H, indazole), 8.00 (dd, J=9.6, 2.2 Hz, 1H, indazole), 7.29 (dt, J=9.1, 2.5 Hz, 1H, indazole), 7.10 (m, 3H, tetrahydroisoquinoline), 7.02 (m, 1H, tetrahydroisoquinoline), 4.05 (s, 2H, Ar--CH2N), 3.68 (s, 2H, Ar--CH2N)), 2.79 (m, 4H, tetrahydroisoquinoline)2.72 (s, 3H, Ac); MS (CI+) m/e 324 (M+H+); Anal. calcd for C19H18FN3O: C, 70.57; H, 5.61; N, 12.99. Found: C, 70.28; H, 5.32; N, 12.84.

Workup

  1. extractionextracted with CH2Cl2 (3×25 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. concentrationconcentrated
  4. customthe residue purified by flash chromatography (7%→12% EtOAc in hexane)

Sources & evidence

ORD record
ord-df7e38bd71d547ed9a6c949d152b978c
Source dataset
uspto-grants-1997_09
Patent number
US05665732

Reaction notes

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