Triethylamine → Trifluoroacetic acid

HRID 713292Notes

Reaction equation

HRID 713292 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[C:28]3[CH2:30][NH:31][CH2:32][CH2:33][C:27]3=[N:26][C:25]=2[NH:34][CH:35]([CH3:37])[CH3:36])[CH2:20][CH2:19]1)[C:12]#[N:13].C(N(CC)CC)C.[CH3:45][O:46][CH2:47][C:48](Cl)=[O:49]>C(Cl)Cl>[F:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][C:16]=1[O:17][CH:18]1[CH2:19][CH2:20][N:21]([C:24]2[N:29]=[C:28]3[CH2:30][N:31]([C:48](=[O:49])[CH2:47][O:46][CH3:45])[CH2:32][CH2:33][C:27]3=[N:26][C:25]=2[NH:34][CH:35]([CH3:37])[CH3:36])[CH2:22][CH2:23]1)[C:12]#[N:13].[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 118159356HCID 118159356, compound

Product 2

HCID 6422Trifluoroacetic acidYield 27.1%HCID 118159268HCID 118159268, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-fluoro-4-((1-(2-(isopropylamino)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-yl)piperidin-4-yl)oxy)benzonitrile 2,2,2-trifluoroacetate (98.6 mg, 0.094 mmol) and triethylamine (0.039 mL, 0.283 mmol) in DCM (1.0 mL) was added methoxyacetyl chloride (0.017 mL, 0.188 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min and then concentrated via rotary evaporation. The crude material was diluted with DMSO, filtered, rinsed with DMSO, and purified by HPLC Method B, with the exception that a Waters XSelect® CSH C18, 5 μm, ID 4.6×50 mm was used, using an ACN gradient of 30% to 70% to give the title compound as a TFA salt (2.9 mg, 5.2%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6, mixture of rotamers) δ ppm 1.18 (d, J=6.6 Hz, 6H), 1.87-1.97 (m, 2H), 2.08-2.16 (m, 2H), 2.62 (t, J=5.8 Hz, 0.9H), 2.72 (t, J=6.1 Hz, 1.1H), 2.89-2.97 (m, 2H), 3.22-3.28 (m, 1H), 3.29 (br s, 1.3H), 3.30 (s, 1.7H), 3.64-3.67 (m, 1.1H), 3.72-3.75 (m, 0.9H), 4.10-4.16 (m, 1H), 4.17 (br s, 0.9H), 4.19 (s, 1.1H), 4.36 (br s, 0.9H), 4.41 (s, 1.1H), 4.80-4.86 (m, 1H), 5.58-5.63 (m, 1H), 7.50 (t, J=8.7 Hz, 1H), 7.66-7.70 (m, 1H), 7.87 (dd, J=11.2, 1.9 Hz, 1H); ESI-MS m/z [M+H]+ 483.5.

Workup

  1. concentrationconcentrated via rotary evaporation
  2. additionThe crude material was diluted with DMSO
  3. filtrationfiltered
  4. washrinsed with DMSO
  5. custompurified by HPLC Method B, with the exception that a Waters XSelect® CSH C18, 5 μm, ID 4.6×50 mm

Sources & evidence

ORD record
ord-2a6aedeb1aab405984671bd4b333cd19
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

Loading…