Sodium Bicarbonate → 2-(6-Fluoro-1H-indazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinoline

HRID 1377513Notes

Reaction equation

C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:13])[CH:11]=2)[C:6]([CH2:14][N:15]2[CH2:24][CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:16]2)=[N:5]1)(=O)C.C[O-].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO>[F:13][C:10]1[CH:11]=[C:12]2[C:7]([C:6]([CH2:14][N:15]3[CH2:24][CH2:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:16]3)=[N:5][NH:4]2)=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 20 °C

Procedure

2-(1-Acetyl-6-fluoro-1H-indazol-3-ylmethyl)-1,2,3,4-tetrahydroisoquinoline (300 mg, 0.93 mmol) in CH2Cl2 /MeOH (1:1, 10 mL) was treated with sodium methoxide (2 mg) and stirred for 15 min at 20° C. The mixture was poured into saturated aqueous sodium bicarbonate solution (25 mL) and extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (MgSO4), concentrated and purified by flash chromatography (50% EtOAc in hexane) to give the title compound as a colourless oil. Conversion to the hydrogen oxalate salt in MeOH/Et2O gave colourless crystals (202 mg, 59%); mp 200°-201° C. (from MeOH/Et2O); 1H NMR (360 MHz, d6 -DMSO) d 7.93 (dd, J=8.8, 5.3 Hz, 1H, indazole), 7.30 (dd, J=9.7, 2.8 Hz, 1H, indazole), 7.15-6.97 (m, 5H, aromatic), 4.25 (s, 2H, Ar--CH2N), 3.88 (s, 2H, Ar--CH2N), 3.00 (bs, 2H, tetrahydroisoquinoline), 2.89 (bs, 2H, tetrahydroisoquinoline); MS (CI+) m/e 282 (M+H+); Anal. calcd for C17H16FN3. (COOH)2. H2O: C, 65.35; H, 5.33; N, 12.71. Found: C, 65.40; H, 5.24; N, 12.49.

Workup

extractionextracted with CH2Cl2 (3×50 mL)
dry with materialThe combined organic extracts were dried (MgSO4)
concentrationconcentrated
custompurified by flash chromatography (50% EtOAc in hexane)

Sources & evidence

ORD record: ord-fcc27fd1c00b411e8f211be92fee90a1
Source dataset: uspto-grants-1997_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05665732

Reaction notes

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