Hydrochloric Acid → HCID 67206644, compound

HRID 2041769Notes

Reaction equation

HRID 2041769 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][N:21](C)[C:22](=O)OC(C)(C)C)[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:30][C:31]2[CH:36]=[N:35][CH:34]=[CH:33][N:32]=2)[CH2:6][C@@H:5]1[CH3:37])(=[O:3])[CH3:2].FC(F)(F)C(O)=O.[ClH:45].CCOCC>ClCCl>[ClH:45].[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[N:16][N:17]([CH2:19][CH2:20][NH:21][CH3:22])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:30][C:31]2[CH:36]=[N:35][CH:34]=[CH:33][N:32]=2)[CH2:6][C@@H:5]1[CH3:37])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 68184866HCID 68184866, compound

Product 1

HCID 67206644HCID 67206644, compoundYield 39.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution 1,1-dimethylethyl (2-{4-[(2S,4R)-1-acetyl-2-methyl-4-(2-pyrazinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-pyrazol-1-yl}ethyl)methylcarbamate (for a preparation see Intermediate 74) (204 mg, 0.403 mmol) in dichloromethane (DCM) (4 mL) was treated with trifluoroacetic acid (TFA) (1 mL, 12.98 mmol) and the resulting mixture was stirred at room temperature for 30 min then concentrated in vacuo. The residue was loaded on a 5 g SCX cartridge then eluted with MeOH (20 mL) followed by 2M NH3 in MeOH (20 mL). The ammonia fractions were combined to give a residue. Purification of this residue on SP4 using a 25 G silica cartridge (gradient:1 to 10% (2M NH3 in MeOH) in DCM) gave a second residue which was purified by MDAP (modifier: formic acid) to give a third residue which was loaded on a 5 g SCX cartridge then eluted with MeOH (20 mL) followed by 2M NH3 in MeOH (20 mL). The ammonia fractions were combined to give a residue which was dissolved in DCM (5 mL). The resulting solution was treated with HCl (1M in Et2O, 0.2 mL, 0.2 mmol) then concentrated in vacuo. Trituration of the residue with Et2O gave (2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methylamino)ethyl]-1H-pyrazol-4-yl}-N-2-pyrazinyl-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (77 mg, 0.159 mmol, 39.3% yield) as a cream solid.

Workup

  1. concentrationthen concentrated in vacuo
  2. washthen eluted with MeOH (20 mL)
  3. customto give a residue
  4. customPurification of this residue on SP4
  5. customgave a second residue which
  6. customwas purified by MDAP (modifier: formic acid)
  7. customto give a third residue which
  8. washthen eluted with MeOH (20 mL)
  9. customto give a residue which
  10. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-cda287b662604fa4b0d5c0cc9ae7eef7
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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