Ammonium Chloride → HCID 59548222, compound

HRID 1812348Notes

Reaction equation

HRID 1812348 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Cl:15][C:16]1[CH:17]=[C:18]([C:23]2[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([NH2:30])[N:24]=2)[C:19](F)=[N:20][CH:21]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH4+].[Cl-]>CN(C=O)C>[NH2:30][C:25]1[N:26]=[C:27]([CH3:29])[N:28]=[C:23]([C:18]2[C:19]([NH:1][C:2]3[CH:3]=[C:4]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])[C:5]([O:8][CH3:9])=[N:6][CH:7]=3)=[N:20][CH:21]=[C:16]([Cl:15])[CH:17]=2)[N:24]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66600424HCID 66600424, compoundHCID 666118184-(5-Chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 59548222HCID 59548222, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N-(5-amino-2-methoxypyridin-3-yl)methanesulfonamide (Step 4, 0.028 g, 0.13 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Step 1, 0.0364 g, 0.152 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 0.52 mL, 0.52 mmol) was added dropwise at 0° C. The solution was stirred at 0° C. for 1.5 h. The reaction mixture was poured into sat'd NH4Cl (15 mL) and stirred. The resulting solid was collected via filtration. The crude product was purified by preparative HPLC (column: Phenomenex, Gemni 5 micron C18 100×30 mm, 10%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The corresponding fractions were combined and concentrated. Sat'd NaHCO3 was added to the residue and sonicated. The resulting yellow solid was collected and washed with water and with MeOH to afford 5 N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)-2-methoxypyridin-3-yl)methanesulfonamide (12.9 mg, 23% yield) as bright yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.76 (s, 1H) 9.27 (s, 1H) 8.72 (d, J=2.54 Hz, 1H) 8.32 (dd, J=10.47, 2.45 Hz, 2H) 8.09 (d, J=2.15 Hz, 1H) 7.77-8.01 (m, 2H) 3.91 (s, 3H) 3.05 (s, 3H) 2.44 (s, 3H). m/z (ESI, positive ion): 436.9 (M+H)+.

Workup

  1. stirringstirred
  2. filtrationThe resulting solid was collected via filtration
  3. customThe crude product was purified by preparative HPLC (column: Phenomenex, Gemni 5 micron C18 100×30 mm, 10%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  4. concentrationconcentrated
  5. additionSat'd NaHCO3 was added to the residue
  6. customsonicated
  7. customThe resulting yellow solid was collected
  8. washwashed with water and with MeOH

Sources & evidence

ORD record
ord-0009ec2d96354dbe9ee71acdb45c6a59
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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