(R)-(+)-1-Boc-3-aminopyrrolidine → HCID 117667150, compound

HRID 1526207Notes

Reaction equation

HRID 1526207 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)=[C:16]([CH3:33])[CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9].[NH2:34][C@@H:35]1[CH2:39][CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36]1>CN1CCCC1=O>[CH2:8]([C:7]1[N:6]=[C:5]([C:10]([NH2:12])=[O:11])[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:21][CH2:22][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:24][CH2:25]3)=[C:16]([CH3:33])[CH:15]=2)=[N:3][C:2]=1[NH:34][C@@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1)[CH3:9]

Participants

4

Reactant 2

HCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 88569548HCID 88569548, compound

Product 1

HCID 117667150HCID 117667150, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 5-chloro-6-ethyl-3-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (200 mg), tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate (360 μL), and N-methylpyrrolidone (0.8 mL) was reacted in a microwave reaction device at 190° C. for 30 minutes. The mixture was subjected to liquid separation by the addition of chloroform and a saturated aqueous sodium hydrogen carbonate solution. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated. To the obtained residue and 1,2-dichloroethane (2.6 mL) were added trifluoroacetic acid (2.6 mL) under ice-cooling, followed by stirring at room temperature for 3 hours. The mixture was diluted with chloroform and neutralized with a 5% aqueous potassium carbonate solution. The organic phase was washed with saturated brine and 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=1:0:0-100:10:1) to obtain 6-ethyl-3-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-[(3R)-pyrrolidin-3-ylamino]pyrazine-2-carboxamide (109 mg) as a pale yellow solid.

Workup

  1. customwas reacted in a microwave reaction device at 190° C. for 30 minutes
  2. customThe mixture was subjected to liquid separation by the addition of chloroform
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated
  7. additionTo the obtained residue and 1,2-dichloroethane (2.6 mL) were added trifluoroacetic acid (2.6 mL) under ice-
  8. temperaturecooling
  9. additionThe mixture was diluted with chloroform
  10. washThe organic phase was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)

Sources & evidence

ORD record
ord-f1b0e991e6714dfe8ebcf9ae9da6dcc8
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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