Ammonium Chloride → N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(2-methoxyethoxy)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide

HRID 1621956Notes

Reaction equation

HRID 1621956 reaction equation
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][C:5]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:25]([Cl:28])=[N:26][CH:27]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH4+].[Cl-]>CN(C=O)C>[NH2:15][C:10]1[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]2[C:2]([NH:21][C:22]3[CH:23]=[C:24]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:25]([Cl:28])=[N:26][CH:27]=3)=[N:3][CH:4]=[C:5]([O:16][CH2:17][CH2:18][O:19][CH3:20])[CH:6]=2)[N:9]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 66612001HCID 66612001, compoundHCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

Product 1

HCID 59548407N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(2-methoxyethoxy)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamideYield 66.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 4-(2-fluoro-5-(2-methoxyethoxy)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.105 g, 0.376 mmol) and N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (Example 330 step 2, 0.0977 g, 0.441 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 1.20 mL, 1.20 mmol) was added slowly at 0° C. The dark brown mixture was stirred at 0° C. for 30 min. Additional NaHMDS (0.5 mL) was added at 0° C. and the stirring was continued at 0° C. for 30 min. The reaction mixture was poured into 30 mL of sat'd NH4Cl and stirred for 30 min. The resulting yellow solid was collected via filtration and washed with copious amount of water and air-dried to afford N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(2-methoxyethoxy)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide (0.120 g, 66% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.96 (s, 1H) 9.62 (s, 1H) 8.61 (d, J=19.95 Hz, 2H) 8.44 (d, J=2.74Hz, 1H) 8.21 (d, J=2.54 Hz, 1H) 7.75-8.01 (m, 2H) 4.12-4.27 (m, 2H) 3.69 (d, J=4.30 Hz, 2H) 3.33 (br. s., 3H) 3.13 (s, 3H) 2.45 (s, 3H). m/z (ESI, positive ion): 481.0 (M+H)+.

Workup

  1. additionwas added slowly at 0° C
  2. waitthe stirring was continued at 0° C. for 30 min
  3. stirringstirred for 30 min
  4. filtrationThe resulting yellow solid was collected via filtration
  5. washwashed with copious amount of water
  6. customair-dried

Sources & evidence

ORD record
ord-7b59c2e1d3aa4317a47b59f7e4faaa01
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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