Sodium Carbonate → HCID 59548252, compound

HRID 1812261Notes

Reaction equation

HRID 1812261 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[C:10]([NH:24][C:25]3[CH:26]=[CH:27][C:28]4[S:32][CH:31]=[N:30][C:29]=4[CH:33]=3)=[N:11][CH:12]=[C:13]([C@H:15]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@@H:18]3[CH3:23])[CH3:16])[CH:14]=2)[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:40][S:41](Cl)(=[O:43])=[O:42]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[C:10]([NH:24][C:25]3[CH:26]=[CH:27][C:28]4[S:32][CH:31]=[N:30][C:29]=4[CH:33]=3)=[N:11][CH:12]=[C:13]([C@H:15]([N:17]3[CH2:22][CH2:21][N:20]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:19][C@@H:18]3[CH3:23])[CH3:16])[CH:14]=2)[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66611170HCID 66611170, compound

Product 1

HCID 59548252HCID 59548252, compoundYield 10.26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((R)-1-((S)-2-methylpiperazin-1-yl)ethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.100 g, 0.217 mmol) in THF (5 mL) was chilled to 0° C. in an ice bath, then sodium carbonate (0.115 g, 1.083 mmol) was added to the mixture while stirring. After 10 min, methanesulfonyl chloride (0.051 mL, 0.650 mmol) was added into the mixture slowly via syringe. After the addition, the ice bath was removed and the mixture was allowed to stir under inert atmosphere overnight. The mixture was diluted with chloroform (20 mL) and water (10 mL). The organic layer was extracted with chloroform (3×10 mL). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated in vacuo. The crude material was adsorbed onto silica gel and purified by chromatography through a silica-gel column (25 g), eluting with a 20% mixture of 10:1 methanol/ammonium hydroxide in dichloromethane to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((R)-1-((S)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)benzo[d]thiazol-5-amine (0.012 g, 0.022 mmol, 10.26% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 12.02 (s, 1H) 8.92 (s, 1H) 8.65 (s, 1H) 8.60 (s, 1H) 8.26 (d, J=2.35 Hz, 1H) 7.79-7.83 (m, 1H) 7.72 (dd, J=8.61, 1.56 Hz, 1H) 5.55 (s, 2H) 4.05 (q, J=7.04 Hz, 1H) 3.21 (s, 2H) 3.11 (s, 1H) 2.87 (s, 2H) 2.61-2.73 (m, 4H) 2.47-2.60 (m, 4H) 1.34-1.46 (m, 3H) 1.02-1.22 (m, 3H). m/z (ESI, +ve ion) 540.0 (M+H)+.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringto stir under inert atmosphere overnight
  4. additionThe mixture was diluted with chloroform (20 mL) and water (10 mL)
  5. extractionThe organic layer was extracted with chloroform (3×10 mL)
  6. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by chromatography through a silica-gel column (25 g)
  10. washeluting with a 20% mixture of 10:1 methanol/ammonium hydroxide in dichloromethane

Sources & evidence

ORD record
ord-3a146ddd623f4034a5bfd1b037092266
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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