Potassium Carbonate → 5-(8-Morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-5-yl)picolinonitrile

HRID 1772714Notes

Reaction equation

HRID 1772714 reaction equation
O[CH2:2][C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[N:9][CH:8]=[C:7]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=3)[N:6]2[CH:25]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[N:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][C:41]=1[SH:50].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([CH:25]=[C:3]([CH2:2][S:50][C:41]4[CH:42]=[CH:43][C:44]5[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=5)[N:40]=4)[N:4]=3)[C:7]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=3)=[CH:8][N:9]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 1177279105-(2-(Hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrileHCID 178418736HCID 178418736, compound

Product 1

HCID 1177277685-(8-Morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-5-yl)picolinonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Compound 75b (70.2 mg, 0.209 mmol) was placed in an 8 mL vial equipped with a stir bar and then DCM (10 mL) and DIEA (72.7 μL, 0.417 mmol) were added. MsCl (24.3 μL, 0.313 mmol) was added, and then the reaction was stirred at rt for 3 days. Additional MsCl (24.3 μL, 0.313 mmol) and DIEA (72.7 μL, 0.417 mmol) were added and the reaction was stirred for 2 h. The solvent was removed under reduced pressure. The crude material was placed in a 50 mL round bottom flask equipped with a stir bar, followed by addition of ACN (25 mL). 2-Quinolinethiol (38.2 mg, 0.230 mmol) and K2CO3 (43.3 mg, 0.313 mmol) were added and then the reaction was stirred at rt for 1 h. The temperature was increased to 80° C. and the reaction was stirred for 18 h. The reaction was cooled to rt, diluted with DCM (20 mL), and filtered. The solvent was removed under reduced pressure. The crude produced was purified by flash column chromatography on silica gel (25-g SiO2 pre-packed column, 0-100% EtOAc/heptanes) to afford compound 75c. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.84 (s, 1H), 7.91 (d, J=8.6 Hz, 1H), 7.81-7.89 (m, 2H), 7.78 (s, 1H), 7.76 (d, J=8.1 Hz, 1H), 7.70 (t, J=7.7 Hz, 1H), 7.60 (d, J=8.1 Hz, 1H), 7.46-7.53 (m, 1H), 7.35 (s, 1H), 7.21 (d, J=8.6 Hz, 1H), 4.69 (s, 2H), 4.30-4.43 (m, 4H), 3.82-3.91 (m, J=4.5, 4.5 Hz, 4H). Mass Spectrum (LCMS, ESI pos.) Calcd. for C26H21N7OS: 480.2 (M+H). found: 480.1.

Workup

  1. customvial equipped with a stir bar
  2. stirringthe reaction was stirred for 2 h
  3. customThe solvent was removed under reduced pressure
  4. customThe crude material was placed in a 50 mL round bottom flask
  5. customequipped with a stir bar
  6. additionfollowed by addition of ACN (25 mL)
  7. stirringthe reaction was stirred at rt for 1 h
  8. temperatureThe temperature was increased to 80° C.
  9. stirringthe reaction was stirred for 18 h
  10. temperatureThe reaction was cooled to rt
  11. filtrationfiltered
  12. customThe solvent was removed under reduced pressure
  13. customThe crude produced
  14. customwas purified by flash column chromatography on silica gel (25-g SiO2 pre-packed column, 0-100% EtOAc/heptanes)

Sources & evidence

ORD record
ord-cbfc3e222c4148f1bedf4bf513edab5d
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

Loading…