1,2-Dichloroethane → tert-butyl 5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1172947Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18]([OH:20])=O)=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=C2N=NN(O)C2=CC=1.O.[Cl:36][C:37]1[CH:38]=[C:39]([CH:44]=[CH:45][C:46]=1[O:47][CH:48]([CH3:50])[CH3:49])/[C:40](=[N:42]/O)/[NH2:41]>CN(C=O)C>[Cl:36][C:37]1[CH:38]=[C:39]([C:40]2[N:42]=[C:18]([C:14]3[CH:13]=[CH:12][CH:11]=[C:10]4[C:15]=3[CH2:16][CH2:17][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]4)[O:20][N:41]=2)[CH:44]=[CH:45][C:46]=1[O:47][CH:48]([CH3:50])[CH3:49]

Participants

Conditions

Temperature: 140 °C

Procedure

To a slurry of 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid (0.380 g, 1.371 mmol) in DMF (1.662 ml) was added EDC (0.263 g, 1.371 mmol) followed by HOBT hydrate. After about 1 h a solution of (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.285 g, 1.246 mmol) in DMF (0.831 ml) was added and the reaction mixture was heated to 140° C. for about 1 hr. The reaction mixture was concentrated in vacuo and purified by chromatography on silica gel to provide tert-butyl 5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.403 g, 69%) as a colorless oil. LCMS (Table 1, Method c) Rt=3.43 min, m/z 471 (M+H)+.

Workup

concentrationThe reaction mixture was concentrated in vacuo
custompurified by chromatography on silica gel

Sources & evidence

ORD record: ord-9d89ea3ce6784aaaa8ff18285f721337
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834039B2

Reaction notes

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