Acetyl chloride → Trifluoroacetic acid

HRID 713285Notes

Reaction equation

HRID 713285 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[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.C(Cl)(=O)C>C(Cl)Cl>[C:2]([N:31]1[CH2:32][CH2:33][C:27]2[C:28](=[N:29][C:24]([N:21]3[CH2:20][CH2:19][CH:18]([O:17][C:16]4[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][C:9]=4[F:8])[CH2:23][CH2:22]3)=[C:25]([NH:34][CH:35]([CH3:37])[CH3:36])[N:26]=2)[CH2:30]1)(=[O:1])[CH3:4].[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 118159356HCID 118159356, compound

Product 2

HCID 6422Trifluoroacetic acidYield 162.3%HCID 118159386HCID 118159386, 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 TFA salt (98.6 mg, 0.094 mmol) and triethylamine (0.039 mL, 0.283 mmol) in DCM (1.0 mL) was added acetyl chloride (0.013 mL, 0.188 mmol) at 0° C. The reaction 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 (8.7 mg, 16%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6, mixture of rotamers) δ ppm 1.18 (d, J=6.6 Hz, 6H), 1.86-1.96 (m, 2H), 2.08 (s, 1.3H), 2.09 (s, 1.7H), 2.10-2.21 (m, 2H), 2.61 (t, J=5.6 Hz, 0.9H), 2.73 (t, J=5.2 Hz, 1.1H), 2.88-2.98 (m, 2H), 3.23-3.31 (m, 2H), 3.66-3.76 (m, 2H), 4.09-4.17 (m, 1H), 4.40 (s, 1.1H), 4.43 (s, 0.9H) 4.80-4.87 (m, 1H), 5.59-5.67 (m, 1H), 7.50 (t, J=8.6 Hz, 1H), 7.68 (dq, J=8.6, 1.7 Hz, 1H), 7.86 (dt, J=11.2, 1.7 Hz, 1H); ESI-MS m/z [M+H]+ 453.5.

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-f033303c82fd46ceb453a4092d125614
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

Loading…