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

HRID 1634081Notes

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 109, 2.6 g, 10.1 mmol) in THF (30 mL) at 0° C. 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 110 (2.14 g, 92%). MS (electrospray) 232.5 (M+1); 1H NMR (CDCl3) δ 1.61 (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-11a814eb98ec438abb2b02145119eae9
Source dataset: uspto-grants-2003_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06506754B1

Reaction notes

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