Potassium Carbonate → tert-Butyl 4-(5-(8-morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 1772657Notes

Reaction equation

HRID 1772657 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]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]4)=[N:21][CH:22]=3)[N:6]2[CH:36]=1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[N:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=[CH:53][C:52]=1[SH:61].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.O.C(#N)C>[O:14]1[CH2:13][CH2:12][N:11]([C:10]2[C:5]3[N:6]([CH:36]=[C:3]([CH2:2][S:61][C:52]4[CH:53]=[CH:54][C:55]5[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=5)[N:51]=4)[N:4]=3)[C:7]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:25][CH2:24]4)=[N:21][CH:22]=3)=[CH:8][N:9]=2)[CH2:16][CH2:15]1

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 117733761tert-Butyl 4-(5-(2-(hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)piperazine-1-carboxylateHCID 178418736HCID 178418736, compound

Product 1

HCID 86345610tert-Butyl 4-(5-(8-morpholino-2-((quinolin-2-ylthio)methyl)imidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of compound 30a (200 mg, 0.40 mmol) in DCM (2 mL) and DIEA (0.15 mL, 0.80 mmol) was cooled to 0° C. and MsCl (47 μL, 0.60 mmol) was added dropwise. The reaction was stirred at 0° C. for 15 min and the solvents were removed under reduced pressure. The residue obtained was treated with ACN (10 mL), 2-quinolinethiol (74 mg, 0.45 mmol) and K2CO3 (84 mg, 0.61 mmol). The resulting mixture was stirred at 60° C. for 20 h. The reaction was diluted with H2O (20 mL) and extracted with DCM (3×30 mL). The combined organic extracts were washed with brine (20 mL) and dried over MgSO4 and filtered. The solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (1:0-0:1 DCM/EtOAc) to obtain compound 30b. Mass Spectrum (LCMS, ESI pos.) Calcd. for C34H38N8O3S: 639.3 (M+H). Found 639.2.

Workup

  1. customthe solvents were removed under reduced pressure
  2. customThe residue obtained
  3. stirringThe resulting mixture was stirred at 60° C. for 20 h
  4. extractionextracted with DCM (3×30 mL)
  5. washThe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customThe solvent was removed under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel (1:0-0:1 DCM/EtOAc)

Sources & evidence

ORD record
ord-ec83d528542648c3842f25dd17cd44b2
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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