N-methyl-2-pyrrolidone → HCID 66940819, compound

HRID 2192467Notes

Reaction equation

HRID 2192467 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([C:12]3[N:16]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[C:19]([Cl:27])[CH:18]=4)[O:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[NH2:37][CH2:38][CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CN1CCCC1=O>CO>[Cl:27][C:19]1[CH:18]=[C:17]([C:15]2[O:14][N:13]=[C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH:5]=[CH:4][N:3]=[C:2]4[NH:37][CH2:38][CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[N:16]=2)[CH:22]=[CH:21][C:20]=1[O:23][CH:24]([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 4192171tert-Butyl 3-aminopropanoateHCID 58149900HCID 58149900, compound

Product 1

HCID 66940819HCID 66940819, compoundYield 14.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
180 °C

Procedure

1-Chloro-5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)isoquinoline (D7; 200 mg, 0.5 mmol), di-isopropylethylamine (0.873 ml, 1.0 mmol) and 1,1-dimethylethyl β-alaninate (726 mg, 5 mmol; available e.g. from Novabiochem) were placed into a 20 ml microwave vial, and N-methyl-2-pyrrolidinone (NMP, 8 ml) was added. The mixture was heated under microwave irradiation at 180° C. for one hour, diluted with methanol and chromatographed over an SCX cation exchange column (Biotage), which was washed with methanol and dichloromethane and eluted with methanolic ammonia. Washings and eluate from the SCX column were re-combined and evaporated in vacuo until only NMP remained. Water (20 ml) was added to the reaction mixture and a solid precipitate formed. The precipitate was collected by filtration and azeotroped twice with toluene. The solid was dissolved in dichloromethane (5 ml) and chromatographed on a silica column, eluting with dichloromethane to yield the title compound (38 mg) as a pale yellow solid.

Workup

  1. customchromatographed over an SCX cation exchange column (Biotage), which
  2. washwas washed with methanol and dichloromethane
  3. washeluted with methanolic ammonia
  4. customevaporated in vacuo until only NMP
  5. additionWater (20 ml) was added to the reaction mixture
  6. customa solid precipitate formed
  7. filtrationThe precipitate was collected by filtration
  8. customazeotroped twice with toluene
  9. dissolutionThe solid was dissolved in dichloromethane (5 ml)
  10. customchromatographed on a silica column
  11. washeluting with dichloromethane

Sources & evidence

ORD record
ord-8b477940815c447fb8d6f493668e23b2
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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