Trifluoroacetic acid → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(imidazo[1,2-b]pyridazin-6-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-one

HRID 1907343Notes

Reaction equation

HRID 1907343 reaction equation
C(O)(C(F)(F)F)=O.[OH:8][C:9]([CH3:31])([CH3:30])[CH2:10][C@@:11]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:16][C:15](=[O:17])[N:14]([C@H:18]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]2)[CH2:13][CH2:12]1.Cl[C:33]1[CH:34]=[CH:35][C:36]2[N:37]([CH:39]=[CH:40][N:41]=2)[N:38]=1.CCN(C(C)C)C(C)C>C(O)(C)C>[OH:8][C:9]([CH3:31])([CH3:30])[CH2:10][C@@:11]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[O:16][C:15](=[O:17])[N:14]([C@H:18]2[CH2:23][CH2:22][CH2:21][N:20]([C:33]3[CH:34]=[CH:35][C:36]4[N:37]([CH:39]=[CH:40][N:41]=4)[N:38]=3)[CH2:19]2)[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 138828Imidazo(1,2-b)pyridazine, 6-chloro-HCID 58278645(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one

Product 1

HCID 66746208(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(imidazo[1,2-b]pyridazin-6-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-oneYield 10.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
160 °C

Procedure

The TFA salt of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one (6 mg, 0.018 mmol), 6-chloroimidazo[1,2-b]pyridazine (6 mg, 2.15 equiv.), and i-Pr2NEt (30 μL, excess) were mixed with isopropanol (1 mL). The mixture was heated in a microwave oven at 160° C. for 2.5 h. After being cooled to rt, the mixture was filtered and purified by prep HPLC to afford the title compound (0.82 mg) as brown oil. LC-MS Method 1 tR=1.07 min., m/z=450 (M+1).

Workup

  1. temperatureAfter being cooled to rt
  2. filtrationthe mixture was filtered
  3. custompurified by prep HPLC

Sources & evidence

ORD record
ord-a811eb186a2a46718ff9d48ad087ce74
Source dataset
uspto-grants-2013_12
Patent number
US08598163B2

Reaction notes

Loading…