Tetrahydrofuran → N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)-5-chloropyridin-2-ylamino)-2-methylpyridin-3-YL)methanesulfonamide

HRID 1812432Notes

Reaction equation

HRID 1812432 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH2:16])[N:10]=2)[C:5](F)=[N:6][CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([CH3:24])=[N:22][CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>CN(C=O)C>[NH2:16][C:11]1[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([C:4]2[C:5]([NH:17][C:18]3[CH:19]=[C:20]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([CH3:24])=[N:22][CH:23]=3)=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:10]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66600561N-(5-amino-2-methylpyridin-3-yl)methanesulfonamideHCID 666118184-(5-Chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 59548192N-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)-5-chloropyridin-2-ylamino)-2-methylpyridin-3-YL)methanesulfonamideYield 113.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 15 mL round-bottom flask was added 4-(5-chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.050 g, 0.209 mmol), N-(5-amino-2-methylpyridin-3-yl)methanesulfonamide (0.046 g, 0.230 mmol), and DMF (2.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (0.169 mL, 0.835 mmol) was then added to the solution in one portion. The now burgundy color mixture was stirred at 0° C. for 10 min then warmed up to rt and stirred for 1 h. The reaction mixture was quenched with sat. NH4Cl and partitioned between water and CHCl3. The aqueous layer was extracted with more CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a yellow solid (100 mg). MS (ESI pos. ion) m/z: 421.0. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.45 (s, 6H) 3.06 (s, 3H) 7.84 (br. s., 1H) 7.97 (br. s., 1H) 8.24 (d, J=2.05 Hz, 1H) 8.38 (d, J=2.63 Hz, 1H) 8.64 (d, J=2.19 Hz, 1H) 8.75 (d, J=2.63 Hz, 1H) 9.32 (br. s., 1H) 11.98 (s, 1H).

Workup

  1. temperaturethen warmed up to rt
  2. stirringstirred for 1 h
  3. customThe reaction mixture was quenched with sat. NH4Cl
  4. custompartitioned between water and CHCl3
  5. extractionThe aqueous layer was extracted with more CHCl3 (2×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (40 g, 3% MeOH in DCM)

Sources & evidence

ORD record
ord-246b4274e50948728f99708f3bfb1cdc
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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