TfOH-TFA → N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)isoquinolin-7-amine

HRID 1812336Notes

Reaction equation

HRID 1812336 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:33][C:34]4[CH:43]=[C:42]5[C:37]([CH:38]=[CH:39][N:40]=[CH:41]5)=[CH:36][CH:35]=4)=[N:18][CH:19]=[C:20]([CH2:22][N:23]4[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]4)[CH:21]=3)[N:10]=2)=CC=1.S(O)(C(F)(F)F)(=O)=O.FC(C(O)=O)(F)F>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:33][C:34]3[CH:43]=[C:42]4[C:37]([CH:38]=[CH:39][N:40]=[CH:41]4)=[CH:36][CH:35]=3)=[N:18][CH:19]=[C:20]([CH2:22][N:23]3[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:27][CH2:28]3)[CH:21]=2)[N:10]=1

Participants

3

Reactant 2

HCID 18539426TfOH-TFAHCID 66600115N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)isoquinolin-7-amine

Product 1

HCID 59548425N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)isoquinolin-7-amineYield 98.4%

Conditions

Temperature
70 °C

Procedure

To a 25 mL, round-bottomed flask was added N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)isoquinolin-7-amine (150 mg, 0.201 mmol) and 5% TfOH-TFA (5 mL). The reaction mixture was stirred at 70° C. for 30 minutes and cooled to room temperature.After removal of TFA in high vacuum, the residue was treated with saturated NaHCO3, the obtained suspension was filtered to provide the crude product as a yellow solid. After air drying, the solid was treated with MeOH-DCM-ether and filtered to provide N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)isoquinolin-7-amine (100 mg, 98% yield) as a yellow solid. m/z (ESI positive ion): 506 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ ppm 2.88 (s, 3H) 3.09-3.16 (m, 4H) 3.29-3.36 (m, 7H) 3.56 (s, 2H) 7.74 (d, J=5.67 Hz, 1H) 7.83 (br s, 1H) 7.93 (d, J=8.80 Hz, 2H) 8.07 (dd, J=8.90, 2.05 Hz, 1H) 8.36 (d, J=5.67 Hz, 1H) 8.40 (d, J=2.15 Hz, 1H) 8.79 (d, J=2.35 Hz, 1H) 8.87 (d, J=1.56 Hz, 1H) 9.21 (s, 1H) 12.42 (s, 1H).

Workup

  1. temperaturecooled to room temperature
  2. customAfter removal of TFA in high vacuum
  3. additionthe residue was treated with saturated NaHCO3
  4. filtrationthe obtained suspension was filtered
  5. customto provide the crude product as a yellow solid
  6. customAfter air drying
  7. additionthe solid was treated with MeOH-DCM-ether
  8. filtrationfiltered

Sources & evidence

ORD record
ord-d143cfd9456f490791aa2f46d290eba1
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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