Hydrochloric Acid → HCID 68161612, compound

HRID 2041766Notes

Reaction equation

HRID 2041766 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]=[C:36]([CH3:38])[CH:35]=[CH:34][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]=[C:36]([CH3:38])[CH:35]=[CH:34][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 86669457HCID 86669457, compound

Product 1

HCID 68161612HCID 68161612, compoundYield 46.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl[2-(4-{(2S,4R)-1-acetyl-2-methyl-4-[(4-methyl-2-pyridinyl)amino]-1,2,3,4-tetrahydro-6-quinolinyl}-1H-pyrazol-1-yl)ethyl]methylcarbamate (for a preparation see intermediate 71) (192.2 mg, 0.371 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 1.5 h 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 and concentrated in vacuo. Purification of the residue on SP4 using a 25 G silica cartridge (gradient:1 to 10% (2M NH3 in MeOH) in DCM) gave a first residue which was purified by MDAP (modifier: formic acid) to give another residue which was dissolved in DCM (5 mL). The resulting solution was treated with HCl (1M in Et2O, 0.22 mL, 0.220 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-(4-methyl-2-pyridinyl)-1,2,3,4-tetrahydro-4-quinolinamine hydrochloride (79.7 mg, 0.171 mmol, 46.1% yield) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-3173ae595d944984a19bad13babf3520
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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