Nitrogen → HCID 67960475, compound

HRID 1529410Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:17]1[N:22]=[C:21]([O:23][C@H:24]2[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:25]32[CH2:27][CH2:26]3)[CH:20]=[N:19][CH:18]=1.[Cl-].[C:40]([O:44][C:45](=[O:48])[CH2:46][Zn+])([CH3:43])([CH3:42])[CH3:41].CCOCC.N#N>O1CCOCC1>[C:40]([O:44][C:45](=[O:48])[CH2:46][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[C:17]1[N:22]=[C:21]([O:23][C@H:24]2[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH2:29][CH2:28][C:25]32[CH2:27][CH2:26]3)[CH:20]=[N:19][CH:18]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of (4R)-tert-butyl 4-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (209 mg, 0.358 mmol), PdCl2(Amphos) (12.66 mg, 0.018 mmol), and (2-tert-butoxy-2-oxoethyl)zinc(II) chloride in Et2O (1073 μL, 0.536 mmol) in dioxane (3576 μL) was heated to 80° C. under a purged stream of N2; the reaction was stirred for 16 h at 80° C. The crude was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% hexanes to 50% EtOAc/hexanes to give (4R)-tert-butyl 4-(6-(5-(2-tert-butoxy-2-oxo ethyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (137 mg, 0.221 mmol, 61.8% yield) as a yellow oil. MS (ESI, pos. ion) m/z: 620.3 (M+1).

Workup

customwas purified

Sources & evidence

ORD record: ord-2f057880effb4c3098e2bda042b276ad
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

Loading…