Pyridine → 1-(3-(cyclobutylamino)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)ethan-1-one

HRID 713360Notes

Reaction equation

HRID 713360 reaction equation
[OH:1][C:2]([C:4](F)(F)F)=O.[CH:8]1([NH:12][C:13]2[N:18]=[C:17]3[CH2:19][NH:20][CH2:21][CH2:22][C:16]3=[N:15][C:14]=2[N:23]2[CH2:28][CH2:27][CH:26]([O:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])[CH2:25][CH2:24]2)[CH2:11][CH2:10][CH2:9]1.N1C=CC=CC=1.C(OC(=O)C)(=O)C>C(Cl)Cl>[CH:8]1([NH:12][C:13]2[N:18]=[C:17]3[CH2:19][N:20]([C:2](=[O:1])[CH3:4])[CH2:21][CH2:22][C:16]3=[N:15][C:14]=2[N:23]2[CH2:28][CH2:27][CH:26]([O:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])[CH2:25][CH2:24]2)[CH2:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 131734048N-cyclobutyl-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt

Product 1

HCID 1181591611-(3-(cyclobutylamino)-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)ethan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-cyclobutyl-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (144 mg, 0.272 mmol) in DCM (2.72 mL) at 0° C. was treated with pyridine (66.0 μL, 0.816 mmol), followed by acetic anhydride (51.3 μL, 0.544 mmol). The reaction mixture was stirred at 0° C. for 2 h. The reaction mixture was concentrated under reduced pressure and taken up in MeOH, filtered through a 0.45 μm Millipore® syringe filter, and purified via HPLC Method A to give the title compound, as a TFA salt, as a yellow solid (74.9 mg, 48.2%). 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 1.82 (m, 2H), 1.97 (m, 2H), 2.11 (m, 4H), 2.19 (s, 1.1H), 2.21 (s, 1.9H), 2.45 (m, 2H), 2.73 (t, J=5.9 Hz, 0.7H), 2.84 (t, J=5.9 Hz, 1.3H), 3.11 (m, 2H), 3.47 (m, 2H), 3.81 (t, J=5.9 Hz, 1.3H), 3.85 (t, J=5.9 Hz, 0.7H), 4.40 (m, 1H), 4.49 (m, 1H), 4.59 (s, 0.7H), 4.63 (s, 1.3H), 6.87 (m, 1H), 6.97 (ddd, J=11.2, 8.5, 3.2 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 458.00.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. filtrationfiltered through a 0.45 μm Millipore® syringe
  3. filtrationfilter
  4. custompurified via HPLC Method A

Sources & evidence

ORD record
ord-e687bd6389374307a56c90dd43dcb52c
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

Loading…