4-Bromo-N,N-dimethylbenzenesulphonamide → 2-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(hydroxy)methyl)-4-bromo-N,N-dimethylbenzenesulfonamide

HRID 1812142Notes

Reaction equation

HRID 1812142 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C([Li])CCC.[CH3:19][O:20][C:21]1[CH:61]=[CH:60][C:24]([CH2:25][N:26]([CH2:51][C:52]2[CH:57]=[CH:56][C:55]([O:58][CH3:59])=[CH:54][CH:53]=2)[C:27]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]([C:34]3[C:35]([NH:42][C:43]4[CH:44]=[N:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=4)=[N:36][CH:37]=[C:38]([CH:41]=3)[CH:39]=[O:40])[N:28]=2)=[CH:23][CH:22]=1>C1COCC1>[CH3:59][O:58][C:55]1[CH:54]=[CH:53][C:52]([CH2:51][N:26]([CH2:25][C:24]2[CH:23]=[CH:22][C:21]([O:20][CH3:19])=[CH:61][CH:60]=2)[C:27]2[N:32]=[C:31]([CH3:33])[N:30]=[C:29]([C:34]3[CH:41]=[C:38]([CH:39]([OH:40])[C:6]4[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=4[S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])[CH:37]=[N:36][C:35]=3[NH:42][C:43]3[CH:44]=[N:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=3)[N:28]=2)=[CH:57][CH:56]=1

Participants

5

Reactant 3

HCID 128184-Bromo-N,N-dimethylbenzenesulphonamideHCID 601552675-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehydeHCID 178418339Butyllithium

Product 1

HCID 666119662-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(hydroxy)methyl)-4-bromo-N,N-dimethylbenzenesulfonamideYield 18.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-bromo-N,N-dimethylbenzenesulfonamide (Aldrich; 152 mg, 0.575 mmol) in THF (1.0 mL) was cooled to −78° C. and treated dropwise with n-butyllithium (1.60 M solution in hexanes) (359 μL, 0.575 mmol). The resulting pale solution was allowed to slowly warm to 0° C. over 30 min to give a dark brown solution which was then added dropwise to a suspension of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (110.7 mg, 0.192 mmol) in THF (2.0 mL) cooled to −78° C. The mixture was stirred for 2 h, slowly allowing to warm to 0° C., and the resulting yellow suspension was quenched (water) and extracted into DCM from saturated aqueous NaHCO3. The extracts were dried (MgSO4), concentrated and purified by flash chromatography (0 to 10 to 20 to 30 to 40% EtOAc in DCM) to give recovered 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (54.6 mg, 49%, eluting off with 20% EtOAc/DCM) followed by 2-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(hydroxy)methyl)-4-bromo-N,N-dimethylbenzenesulfonamide (30.0 mg, 0.036 mmol, 18.60% yield) (eluting off with 30% EtOAc/DCM) followed by 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(hydroxy)methyl)-N,N-dimethylbenzenesulfonamide (38.3 mg, 0.050 mmol, 26.2% yield) (eluting off with 40% EtOAc/DCM).

Workup

  1. customto give a dark brown solution which
  2. temperaturecooled to −78° C
  3. temperatureto warm to 0° C.
  4. customthe resulting yellow suspension was quenched (water)
  5. extractionextracted into DCM from saturated aqueous NaHCO3
  6. dry with materialThe extracts were dried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by flash chromatography (0 to 10 to 20 to 30 to 40% EtOAc in DCM)
  9. customto give
  10. customrecovered 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (54.6 mg, 49%, eluting off with 20% EtOAc/DCM)

Sources & evidence

ORD record
ord-e5e3be355e2247ec8fcf919c25554c6c
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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