Potassium Carbonate → Tert-butyl 3-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1h)-yl)propanoate

HRID 1172950Notes

Reaction equation

HRID 1172950 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH2:19][CH2:20][NH:21][CH2:22]4)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([O-])([O-])=O.[K+].[K+].Br[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH2:19][CH2:20][N:21]([CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:22]4)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 256128tert-Butyl 3-bromopropionate4×HCID 595566813-(3-Chloro-4-isopropoxyphenyl)-5-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1,2,4-oxadiazole

Product 1

HCID 59556729Tert-butyl 3-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1h)-yl)propanoateYield 66.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(3-chloro-4-isopropoxyphenyl)-5-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1,2,4-oxadiazole (0.1088 g, 0.294 mmol) in DMF (2.94 ml) (briefly heated to 40° C. for complete dissolution). K2CO3 (0.081 g, 0.588 mmol) and tert-butyl 3-bromopropanoate (0.046 ml, 0.276 mmol) was added and the mixture stirred at ambient temperature for 2 hrs. Additional tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol) was added and the reaction was stirred at 60° C. over the weekend. Additional tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol) was added and the reaction continued heated at 60° C. overnight. Additional K2CO3 (0.041 g, 0.294 mmol) was added, followed by tert-butyl 3-bromopropanoate (0.053 ml, 0.315 mmol). The reaction was heated at 60° C. overnight. The reaction mixture was filtered and the filtrate concentrated in vacuo to give ˜179 mg of crude yellow oil. The crude residue was purified via Analogix system using RediSep RS 12 g column, with a gradient of 0-45% EtOAc/Heptane over 35 min. at 15 mL/min. Fractions 23-28 were combined and concentrated to yield tert-butyl 3-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)propanoate (91 mg, 0.183 mmol) as light yellow oil. LCMS (Table 1, Method c) Rt=3.39 min, m/z 500.72 (M+H)+.

Workup

  1. stirringthe reaction was stirred at 60° C. over the weekend
  2. temperaturethe reaction continued heated at 60° C. overnight
  3. temperatureThe reaction was heated at 60° C. overnight
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe filtrate concentrated in vacuo
  6. customto give ˜179 mg of crude yellow oil
  7. customThe crude residue was purified via Analogix system
  8. waitwith a gradient of 0-45% EtOAc/Heptane over 35 min. at 15 mL/min
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d7cfa921577646cbac68c2203a78a3d6
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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