Trifluoroacetic acid → HCID 49785832, compound

HRID 1622002Notes

Reaction equation

HRID 1622002 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:18]=3)=[CH:15][C:14]([C@H:43]([N:45]3[CH2:50][CH2:49][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:47][C@H:46]3[CH3:55])[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:15][C:14]([C@H:43]([N:45]3[CH2:50][CH2:49][N:48]([S:51]([CH3:54])(=[O:53])=[O:52])[CH2:47][C@H:46]3[CH3:55])[CH3:44])=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 62406Trifluoromethanesulfonic acidHCID 66611581HCID 66611581, compound

Product 1

HCID 49785832HCID 49785832, compoundYield 52.5%

Conditions

Temperature
70 °C

Procedure

To a 50-mL round-bottomed flask was added 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((R)-1-((R)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.130 g, 0.168 mmol), 2,2,2-trifluoroacetic acid (5 mL, 0.842 mmol), and trifluoromethanesulfonic acid (0.2 mL, 0.168 mmol).The solution was stirred at 70° C. for 30 minutes. The volatiles were removed under a vacuum and the residue was cooled in ice bath and neutralized with 1 N NaOH. The mixture was stirred at room temperature overnight and the precipitate was filtered and washed with water. The precipitate was purified with preparative TLC using 5% (MeOH in DCM). The sample dried overnight under high vacuum to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-((R)-1-((R)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.047 g, 0.088 mmol, 52.5% yield). m/z (ESI, positive ion) 532.2 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (d, J=6.26 Hz, 3H) 1.38 (d, J=6.65Hz, 3H) 2.45 (m, 4H) −2.55 (m, 1H) 2.84 (s, 5H) 3.01-3.18 (m, 3H) 3.94 (s, 3H) 4.00 (d, J=6.85 Hz, 1H) 7.74-7.78 (m, 1H) 7.88-7.92 (m, 1H) 8.31-8.34 (m, 1H) 8.37-8.43 (m, 2H) 8.70-8.74 (m, 1H) 11.93 (s, 1H).

Workup

  1. customThe volatiles were removed under a vacuum
  2. temperaturethe residue was cooled in ice bath
  3. stirringThe mixture was stirred at room temperature overnight
  4. filtrationthe precipitate was filtered
  5. washwashed with water
  6. customThe precipitate was purified with preparative TLC
  7. customThe sample dried overnight under high vacuum

Sources & evidence

ORD record
ord-533c8d60f0e84ed8a5ca2afff153d981
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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