Pyridine → HCID 118159206, compound

HRID 713363Notes

Reaction equation

HRID 713363 reaction equation
[OH:1][C:2]([C:4](F)(F)F)=O.[C@@H:8]([NH:12][C:13]1[N:18]=[C:17]2[CH2:19][NH:20][CH2:21][CH2:22][C:16]2=[N:15][C:14]=1[N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[CH2:25][CH2:24]1)([CH2:10][CH3:11])[CH3:9].N1C=CC=CC=1.C(OC(=O)C)(=O)C>C(Cl)Cl>[C@@H:8]([NH:12][C:13]1[N:18]=[C:17]2[CH2:19][N:20]([C:2](=[O:1])[CH3:4])[CH2:21][CH2:22][C:16]2=[N:15][C:14]=1[N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:37])[CH2:25][CH2:24]1)([CH2:10][CH3:11])[CH3:9]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 131734050HCID 131734050, compound

Product 1

HCID 118159206HCID 118159206, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)—N-(sec-butyl)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (169.0 mg) in DCM (3.18 mL) at 0° C. was treated with pyridine (0.077 mL, 0.954 mmol), followed by acetic anhydride (0.060 mL, 0.636 mmol). The reaction mixture was stirred for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was taken up in MeOH, filtered through a Millipore® 0.45 μm syringe filter, and purified by HPLC Method A to give the title compound, as a TFA salt, as a yellow semisolid (84.9 mg, 43.4% over two steps). 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 0.98 (m, 3H), 1.27 (m, 3H), 1.68 (m, 2H), 1.97 (m, 2H), 2.13 (m, 2H), 2.19 (s, 1.1H), 2.21 (s, 1.9H), 2.74 (td, J=5.9, 1.5 Hz, 0.7H), 2.84 (td, J=5.9, 1.5 Hz, 1.3H), 3.11 (m, 2H), 3.45 (m, 2H), 3.82 (t, J=5.9 Hz, 1.3H), 3.86 (m, 0.7H), 3.97 (m, 1H), 4.50 (m, 1H), 4.61 (d, J=3.9 Hz, 0.7H), 4.64 (s, 1.3H), 6.87 (m, 1H), 6.97 (ddd, J=11.3, 8.7, 2.9 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 460.00.

Workup

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

Sources & evidence

ORD record
ord-6706105e44e5451789e6349726d950fb
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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