Trifluoroacetic acid → 1'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618752Notes

Reaction equation

HRID 1618752 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:27]1[C:35]3[C:30](=[N:31][CH:32]=[C:33]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH:34]=3)[C:29]3([CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[CH2:28]1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]1)=[N:7]2.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:27]1[C:35]3[C:30](=[N:31][CH:32]=[C:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)[CH:34]=3)[C:29]3([CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)[CH2:28]1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[N:7]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67285378US8765940, tert-butyl 4-(5,7-difluoro-3-methyl-4-(6'-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridin]-1'(2'H)-yl)-2-quinolinyl)-1-piperazinecarboxylate

Product 1

HCID 672844611'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Tert-Butyl 4-(5,7-difluoro-3-methyl-4-(6′-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-1′(2′H)-yl)-2-quinolinyl)-1-piperazinecarboxylate (450 mg, 0.70 mmol) was dissolved in DCM (5.0 mL) and cooled to 0° C. TFA (5.0 mL, 65.0 mmol) was then added and the reaction mixture was allowed to warm to rt and stirred for 2.5 h. The reaction was diluted with DCM and concentrated to dryness. The residue was then converted to the free amine by eluting through an SCX column with 0 to 2M ammonia in MeOH to give 1′-(5,7-difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 7.56 (1H, d, J=2.3 Hz), 7.36 (1H, ddd, J=9.9, 2.5, 1.3 Hz), 6.73 (1H, ddd, J=11.8, 9.1, 2.5 Hz), 5.66 (1H, d, J=2.3 Hz), 4.04-4.21 (2H, m), 3.80-3.97 (2H, m), 3.70-3.79 (4H, m), 3.56 (2H, qd, J=11.6, 2.4 Hz), 3.27-3.46 (4H, m), 3.02-3.18 (4H, m), 2.90-3.02 (4H, m), 2.26-2.38 (2H, m), 2.24 (3H, s), 1.97 (1H, br. s.), 1.79 (1H, d, J=13.3 Hz), 1.70 (1H, dd, J=13.6, 1.9 Hz). Mass Spectrum (ESI) m/e=537.3 (M+1).

Workup

  1. temperatureto warm to rt
  2. concentrationconcentrated to dryness
  3. washby eluting through an SCX column with 0 to 2M ammonia in MeOH

Sources & evidence

ORD record
ord-db91f90fe02c4014802c662d395d2de1
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

Loading…