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Trifluoromethanesulfonic acid → N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)acetamide

HRID 1621684
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HRID 1621684 반응식
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:23][C:24]4[CH:25]=[CH:26][C:27]([NH:30][C:31](=[O:33])[CH3:32])=[N:28][CH:29]=4)=[N:18][CH:19]=[C:20]([Cl:22])[CH:21]=3)[N:10]=2)=CC=1.FC(F)(F)S(O)(=O)=O>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:23][C:24]3[CH:25]=[CH:26][C:27]([NH:30][C:31](=[O:33])[CH3:32])=[N:28][CH:29]=3)=[N:18][CH:19]=[C:20]([Cl:22])[CH:21]=2)[N:10]=1
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참가 물질

4

반응물 2

HCID 62406Trifluoromethanesulfonic acidHCID 66610813HCID 66610813, 화합물

생성물 1

HCID 59548295N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)acetamide수율 47.6%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

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온도
75 °C

실험 절차

A solution of N-(5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)acetamide (0.060 g, 0.098 mmol) and trifluoromethanesulfonic acid (TCI) (40 μL, 0.450 mmol) in TFA (2 mL) was stirred at rt for 2.5 h. Then the mixture was stirred at 75° C. for 2 h. Most of the TFA was removed in vacuo and then the residue was taken up in a small amount of DCM. Solid NaHCO3 was added in portions until no more effervescence was observed. Water was added and the resulting solid was collected by filtration. The crude product was purified by preparative HPLC using Phenomenex, Gemni 5 micron C18 100×30 mm column (0%-10% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The fractions containing product formed a precipitate which was collected by filtration and dried in a vacuum oven to give N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)acetamide (0.0173 g, 36% yield) as a yellow solid. 1H NMR (300 MHz, d6-DMSO) δ 11.87 (s, 1H); 10.43 (s, 1H); 8.67-8.78 (m, 2H); 8.37 (br. s., 1H); 8.15-8.24 (m, 1H); 7.93-8.07 (m, 2H); 7.84 (br. s., 1H); 2.45 (s, 3H); 2.09 (s, 3H). m/z (ESI, +ve ion) 371.0 (M+H)+.

후처리

  1. customMost of the TFA was removed in vacuo
  2. additionSolid NaHCO3 was added in portions until no more effervescence
  3. additionWater was added
  4. filtrationthe resulting solid was collected by filtration
  5. customThe crude product was purified by preparative HPLC
  6. customC18 100×30 mm column (0%-10% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  7. additionThe fractions containing product
  8. customformed a precipitate which
  9. filtrationwas collected by filtration
  10. customdried in a vacuum oven

출처 및 근거

ORD 기록
ord-c5619691d9884f0399aae46cd053422b
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08772480B2

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