Dimethyl Sulfoxide → HCID 58204782, compound

HRID 1629495Notes

Reaction equation

Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:18]([CH:19]([CH3:21])[CH3:20])[N:17]=[CH:16][N:15]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.O[C@H:25]1[CH2:29][NH:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:41]S(C)=O>[Cu]I>[CH:19]([N:18]1[C:14]([C:12]2[N:13]=[C:6]3[N:7]([CH2:8][CH2:9][O:10][C:4]4[CH:3]=[C:2]([N:28]5[CH2:29][CH2:25][CH2:41][CH2:26][CH:27]5[C:30]([OH:32])=[O:31])[CH:23]=[CH:22][C:5]=43)[CH:11]=2)=[N:15][CH:16]=[N:17]1)([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 80 °C

Procedure

9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 194 (1.01 g, 2.7 mmol), methyl piccolinate (3.86 g, 27.0 mmol), copper (I) iodide (0.2 g, 1.08 mmol), trans-4-hydroxy(L)proline (0.14 g, 1.08 mmol) and potassium phosphate (1.14 g, 5.4 mmol) in DMSO (10 mL) were heated at 80° C. for 24 hours. The cooled reaction mixture was loaded onto an Isolute SCX-2 cartridge, washed with methanol and eluted with 2M ammonia in methanol. The resultant residue was triturated with diethyl ether to afford 1-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidine-2-carboxylic acid (1.04 g, 87% total). LCMS: RT=2.94 min, [M+H]+=423.

Workup

customThe cooled reaction mixture
washwashed with methanol
washeluted with 2M ammonia in methanol
customThe resultant residue was triturated with diethyl ether

Sources & evidence

ORD record: ord-d0ea03ada71c4dc7a45db6c4d0bd34f3
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785626B2

Reaction notes

Loading…