Pyridine → HCID 118159327, compound

HRID 713353Notes

Reaction equation

HRID 713353 reaction equation
[OH:1][C:2]([C:4](F)(F)F)=O.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@@H:16]([F:37])[CH:17]1[CH2:22][CH2:21][N:20]([C:23]2[N:24]=[C:25]3[CH2:36][CH2:35][NH:34][CH2:33][C:26]3=[N:27][C:28]=2[NH:29][CH:30]([CH3:32])[CH3:31])[CH2:19][CH2:18]1.C(OC(=O)C)(=O)C.N1C=CC=CC=1>C(Cl)Cl>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@@H:16]([F:37])[CH:17]1[CH2:22][CH2:21][N:20]([C:23]2[N:24]=[C:25]3[CH2:36][CH2:35][N:34]([C:2](=[O:1])[CH3:4])[CH2:33][C:26]3=[N:27][C:28]=2[NH:29][CH:30]([CH3:32])[CH3:31])[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 131734044HCID 131734044, compound

Product 1

HCID 118159327HCID 118159327, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-(4-((2,4-difluorophenyl)fluoromethyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (56.0 mg, 0.105 mmol) in DCM (1.05 mL) at 0° C. was treated with acetic anhydride (19.8 μL, 0.210 mmol) and pyridine (25.5 μL, 0.315 mmol). The reaction mixture was concentrated under reduced pressure, taken up in MeOH, filtered, and purified by HPLC Method B. Fractions containing product were concentrated under reduced pressure. The material was repurified by HPLC Method A to give the title compound, as a TFA salt, as a pale yellow solid (5.4 mg, 8.9%). 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 1.31 (m, 6H), 1.45 (d, J=11.7 Hz, 1H), 1.67 (m, 2H), 2.00 (m, 1H), 2.11 (m, 1H), 2.19 (s, 1.1H), 2.21 (s, 1.9H), 2.80 (m, 4H), 3.53 (m, 2H), 3.82 (t, J=5.9 Hz, 1.3H), 3.86 (t, J=5.9 Hz, 0.7H), 4.11 (m, 1H), 4.60 (s, 0.7H), 4.64 (s, 1.3H), 5.53 (m, 1H), 7.02 (m, 2H), 7.50 (m, 1H); ESI-MS m/z [M+H]+ 462.5.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. filtrationfiltered
  3. custompurified by HPLC Method B
  4. additionFractions containing product
  5. concentrationwere concentrated under reduced pressure
  6. customThe material was repurified by HPLC Method A

Sources & evidence

ORD record
ord-eb95afec1e054ba58a2bba60d1ab173b
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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