N-methyl-2-pyrrolidone → HCID 117675614, compound

HRID 1526208Notes

Reaction equation

HRID 1526208 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:27][CH2:26][C:21]4([O:25][CH2:24][CH2:23][O:22]4)[CH2:20][CH2:19]3)=[C:14]([CH3:28])[CH:13]=2)[C:5]([C:8]([NH2:10])=[O:9])=[N:6][CH:7]=1.[NH2:29][C@@H:30]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]1.CN1CCCC1=O.C(=O)([O-])O.[Na+]>O>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:29][C@@H:30]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]2)=[N:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:27][CH2:26][C:21]3([O:25][CH2:24][CH2:23][O:22]3)[CH2:20][CH2:19]2)=[C:14]([CH3:28])[CH:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 516892Sodium BicarbonateHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 88569755HCID 88569755, compound

Product 1

HCID 117675614HCID 117675614, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 5-chloro-3-{[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-methylphenyl]amino}pyrazine-2-carboxamide (1.7 g), tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate (3.57 mL), and N-methylpyrrolidone (10.8 mL) was reacted in a microwave reaction device at 190° C. for 60 minutes. The reactant was left to be cooled, and then water and a saturated aqueous sodium hydrogen carbonate solution were added thereto, followed by extraction with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-500:10:1) to obtain tert-butyl (3R)-3-[(5-carbamoyl-6-{[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-methylphenyl]amino}pyrazin-2-yl)amino]pyrrolidine-1-carboxylate (1.71 g) as a yellow amorphous substance.

Workup

  1. customwas reacted in a microwave reaction device at 190° C. for 60 minutes
  2. waitThe reactant was left
  3. temperatureto be cooled
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-500:10:1)

Sources & evidence

ORD record
ord-7cb9d0b6f35441068369b7665a73796e
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

Loading…