Hydrochloric Acid → HCID 67206339, compound

HRID 2041768Notes

Reaction equation

HRID 2041768 reaction equation
CC([CH2:5][N:6]([CH2:10][CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]([C:27](=[O:29])[CH3:28])[C@@H:22]([CH3:30])[CH2:21][C@H:20]3[NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[N:33]=2)[CH:14]=[N:13]1)C(=O)[O-])(C)C.FC(F)(F)C(O)=O.[ClH:46].CCOCC>ClCCl>[ClH:46].[C:27]([N:23]1[C:24]2[C:19](=[CH:18][C:17]([C:15]3[CH:14]=[N:13][N:12]([CH2:11][CH2:10][NH:6][CH3:5])[CH:16]=3)=[CH:26][CH:25]=2)[C@H:20]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[N:33]=2)[CH2:21][C@@H:22]1[CH3:30])(=[O:29])[CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 86669459HCID 86669459, compound

Product 1

HCID 67206339HCID 67206339, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl[2-(4-{(2S,4R)-1-acetyl-4-[(6-fluoro-2-pyridinyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl}-1H-pyrazol-1-yl)ethyl]methylcarbamate (for a preparation see intermediate 73) (260.2 mg, 0.498 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 45 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 which was purified by MDAP (modifier: formic acid) to give a second residue which was dissolved in DCM (5 mL). The resulting solution was treated with HCl (1M in Et2O, 0.24 mL, 0.24 mmol) then concentrated in vacuo. Trituration of the residue with Et2O gave (2S,4R)-1-acetyl-N-(6-fluoro-2-pyridinyl)-2-methyl-6-{1-[2-(methylamino)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (100.6 mg, 0.201 mmol, 40.4% yield) as a white solid.

Workup

  1. concentrationthen concentrated in vacuo
  2. washthen eluted with MeOH (20 mL)
  3. customto give a residue which
  4. customwas purified by MDAP (modifier: formic acid)
  5. customto give a second residue which
  6. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-4a515c496ab24626b802cd58712b12ca
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

Loading…