Trifluoroacetic acid → (S)-4-(2-fluoro-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1812205Notes

Reaction equation

HRID 1812205 reaction equation
[CH3:1][O:2][C:3]1[CH:48]=[CH:47][C:6]([CH2:7][N:8]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([CH2:23][N:24]4[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][C@@H:25]4[CH3:37])[CH:19]=[N:20][C:21]=3[F:22])[N:10]=2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O.[CH3:56][S:57](Cl)(=[O:59])=[O:58]>C(Cl)Cl>[F:22][C:21]1[C:16]([C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[CH2:7][C:6]3[CH:47]=[CH:48][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:10]=2)=[CH:17][C:18]([CH2:23][N:24]2[CH2:29][CH2:28][N:27]([S:57]([CH3:56])(=[O:59])=[O:58])[CH2:26][C@@H:25]2[CH3:37])=[CH:19][N:20]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 31297Methanesulfonyl chlorideHCID 66611415(S)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)-3-methylpiperazine-1-carboxylate

Product 1

HCID 66611277(S)-4-(2-fluoro-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 135.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirred solution of (S)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)-3-methylpiperazine-1-carboxylate (10.386 g, 15.79 mmol) in DCM (25.0 mL, 389 mmol) was cooled in an ice bath and slowly treated with TFA (25.0 mL, 324 mmol). The resulting mixture was stirred at room temperature for 1 h and then concentrated. The sticky residue was taken up in DCM (100 mL) and cooled to −45° C. TEA (22.0 mL, 158 mmol) was then added via additional funnel, followed by slow addition of methanesulfonyl chloride (6.15 mL, 79 mmol) in DCM (20 mL). The heterogeneous mixture was stirred at −30° C. for 30 min and then quenched with water and NH4Cl(aq) (50 mL each). The organic layer was separated, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were then washed with brine, dried over Na2SO4, and concentrated to give (S)-4-(2-fluoro-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (13.6 g crude) as a pale-yellow foam, which was taken directly to the next step without further purification. m/z (ESI, +ve ion) 636 (M+H)+.

Workup

  1. concentrationconcentrated
  2. temperaturecooled to −45° C
  3. stirringThe heterogeneous mixture was stirred at −30° C. for 30 min
  4. customquenched with water and NH4Cl(aq) (50 mL each)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with DCM (2×50 mL)
  7. washThe combined organic layers were then washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c25ff8cf420342c685d4bad70d339418
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…