Ethyl Acetate → 5-(Aminomethyl)-1-(2-tetrahydropyranyl)indazole

HRID 1263435Notes

Reaction equation

[H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]([CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[N:15]=[CH:14]2)=[N+]=[N-].[OH-].[Na+].C(OCC)(=O)C>C1COCC1>[NH2:7][CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[N:15]=[CH:14]2

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of LiAlH4 (Aldrich, 10.5 mL, 10.5 mmol, 1.0 M) in THF was added dropwise into a yellow solution of 5-(azidomethyl)-1-(2-tetrahydropyranyl)indazole (compound 94, 2.6 g, 10.1 mmol) in THF (30 mL) at 0° C. The addition time was 10 minutes and gas was released. After stirring at 0° C. for 1 hour, NaOH (1.0M, 1.5 mL) was added. The reaction mixture was allowed to warm to room temperature. Ethyl acetate (100 mL) was added, and the suspension was filtered (Celite). The filter cake was washed with an addition portion of ethyl acetate (40 mL). Combined organic layers were evaporated under vacuum to give free amine 63 (2.14 g, 92%). MS (electrospray) 232.5 (M+1); 1H NMR (CDCl3) δ1.61 (m, 3H), 2.02 (m, 2H), 2.50 (m, 1H), 2.83 (br s, 2H), 3.68 (m, 1H), 3.85 (s, 2H), 3.95 (m, 1H), 5.62 (d, 1H, J=9.2 Hz), 7.29 (d, 1H, J=8.8 Hz), 7.48 (d, 1H, J=8.8 Hz), 7.53 (s, 1H), 7.92 (s, 1H).

Workup

temperatureto warm to room temperature
filtrationthe suspension was filtered (Celite)
washThe filter cake was washed with an addition portion of ethyl acetate (40 mL)
customCombined organic layers were evaporated under vacuum

Sources & evidence

ORD record: ord-c401f4100e1347e190f3b89154f0a616
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06541467B1

Reaction notes

Loading…