Methanesulfonyl chloride → HCID 178492163, compound

HRID 1621467Notes

Reaction equation

HRID 1621467 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)=[CH:14][C:13]([CH2:26][N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[CH:12][N:11]=2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>[NH4+].[Cl-].O.C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)=[CH:14][C:13]([CH2:26][N:27]3[CH2:28][CH2:29][N:30]([S:43]([CH3:42])(=[O:45])=[O:44])[CH2:31][CH2:32]3)=[CH:12][N:11]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178492161HCID 178492161, compound

Product 1

HCID 178492163HCID 178492163, compoundYield 16%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

The crude residue from Step 1 was taken up in DCM (3 mL, 46.6 mmol), cooled to 0° C. and then DIEA (0.132 mL, 0.755 mmol) and methanesulfonyl chloride (0.029 mL, 0.378 mmol) were added. The mixture was stirred at the same temperature for 1 h and then diluted with NH4Cl(aq) and water (10 mL each) and diluted with DCM (10 mL). The separated aqueous layer was extracted with DCM (2×15 mL) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and chromatographed through a Redi-Sep pre-packed silica gel column (DCM to 10% MeOH in DCM) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine (21 mg, 16%) as a yellow solid. LCMS (API-ES) m/z 510 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 13.58 (br. s., 1H) 12.62 (br. s., 1H) 9.73 (br. s., 1H) 8.62 (s, 1H) 8.54 (d, J=2.54 Hz, 1H) 8.22 (d, J=1.56 Hz, 1H) 8.18 (dd, J=8.90, 2.45 Hz, 1H) 6.85 (d, J=8.80 Hz, 1H) 3.85 (s, 3H) 3.56 (s, 2H) 3.01-3.18 (m, 4H) 2.86 (s, 3H) 2.86 (s, 3H) 2.53 (br. s., 4H).

Workup

  1. extractionThe separated aqueous layer was extracted with DCM (2×15 mL)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customchromatographed through a Redi-Sep pre-packed silica gel column (DCM to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-4dba8bb60c1a40019aa4c110f66ef801
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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