Ammonia → HCID 89815316, compound

HRID 525338Notes

Reaction equation

HRID 525338 reaction equation
[NH3:1].[N:2]1[N:3]=[CH:4][N:5]2[C:10]=1[CH:9]=[CH:8][C:7]([C:11]1[CH:12]=[C:13]([C:18]3[CH:23]=[CH:22][C:21]([N:24]4[C@@H:28]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[C:27]([CH3:36])([CH3:35])[O:26][C:25]4=[O:37])=[CH:20][CH:19]=3)[CH:14]=[N:15][C:16]=1F)=[N:6]2>CS(C)=O>[N:2]1[N:3]=[CH:4][N:5]2[C:10]=1[CH:9]=[CH:8][C:7]([C:11]1[CH:12]=[C:13]([C:18]3[CH:23]=[CH:22][C:21]([N:24]4[C@@H:28]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[C:27]([CH3:36])([CH3:35])[O:26][C:25]4=[O:37])=[CH:20][CH:19]=3)[CH:14]=[N:15][C:16]=1[NH2:1])=[N:6]2

Participants

4

Reactant 2

HCID 222AmmoniaHCID 89815633HCID 89815633, compound

Product 1

HCID 89815316HCID 89815316, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A 2-mL glass microwave reaction vessel was charged with ammonia (2 M solution in 2-propanol) (63.2 μL, 2.91 mmol) (commercially available from Sigma-Aldrich, Milwaukee, Wis.) and (S)-3-(4-(5-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-6-fluoropyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (14 mg, 0.029 mmol) in DMSO (291 μL). The reaction mixture was stirred and heated at 120° C. overnight. LC-MS indicated clean and complete conversion to desired product. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with water (2×) and brine and dried over MgSO4. The solution was filtered and concentrated under reduced pressire. The residue was purified by reverse-phase preparative HPLC using 0.1% TFA in ACN/H2O, gradient 15% to 90% over 20 minutes to provide (S)-3-(4-(5-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-6-aminopyridin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.44 (d, J=2.24 Hz, 1H), 8.39 (d, J=9.72 Hz, 1H), 8.27 (d, J=2.56 Hz, 1H), 8.03 (d, J=9.94 Hz, 1H), 7.67 (d, J=8.76 Hz, 2H), 7.55 (d, J=8.87 Hz, 2H), 7.35-7.41 (m, 2H), 7.27-7.34 (m, 3H), 7.23 (s, 2H), 5.47-5.53 (m, 1H), 1.66 (s, 3H), 0.92 (s, 3H). m/z (ESI) 478.2 (M+H)+.

Sources & evidence

ORD record
ord-486b7f77b101412783e7b614bf1856c7
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

Loading…