Trifluoroacetic acid → N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)benzo[d]thiazol-5-amine

HRID 1812155Notes

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:35]=[CH:36][C:37]5[S:41][CH:40]=[N:39][C:38]=5[CH:42]=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.FC(F)(F)C(O)=O>>[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:35]=[CH:36][C:37]4[S:41][CH:40]=[N:39][C:38]=4[CH:42]=3)=[N:18][CH:19]=[C:20]([CH2:22][N:23]3[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:25][CH2:24]3)[CH:21]=2)[N:10]=1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 66611977N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)benzo[d]thiazol-5-amine

Product 1

HCID 59548398N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)benzo[d]thiazol-5-amineYield 52.3%

Conditions

Temperature: 120 °C

Procedure

A microwave vial (5 mL) was charged with 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)benzo[d]thiazol-5-amine (45.0 mg, 0.060 mmol) in trifluoroacetic acid (Aldrich, St. Louis, Mo.) (1.50 mL, 20.19 mmol). The mixture was heated in a microwave at 120° C. for 45 min, and then the solvent was removed in vacuo. The residue was purified with reverse phase preperative HPLC using a Phenomenex Gemini columb, 5 micron, C18, 100 Å, 150×30 mm (eluting with 10% to 55% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 45 mL/min) to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)benzo[d]thiazol-5-amine (16.0 mg, 0.031 mmol, 52.3% yield) as a yellow solid after solvent removal and neutralization. 1H NMR (400 MHz, d6-DMSO) δ 12.23 (1H, s); 9.35 (1H, s); 8.90 (1H, d, J=1.8 Hz); 8.76 (1H, d, J=2.0 Hz); 8.34 (1H, d, J=2.0 Hz); 8.06 (1H, d, J=8.8 Hz); 7.91 (1H, br. s.); 7.72-7.86 (2H, m); 3.53 (2H, s); 3.12 (4H, d, J=4.1 Hz); 2.87 (3H, s); 2.48 (7H, br. s.). m/z (ESI, +ve ion) 512 (M+H)+.

Workup

customthe solvent was removed in vacuo
customThe residue was purified with reverse phase preperative HPLC
washeluting with 10% to 55% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 45 mL/min)

Sources & evidence

ORD record: ord-d1a19fd74bca46919b62e5f452abcc50
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362241B2

Reaction notes

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