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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
ノート
印刷プレビュー

反応式

HRID 1621684 の反応式
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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 62406Trifluoromethanesulfonic acidHCID 66610813HCID 66610813、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
75 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-c5619691d9884f0399aae46cd053422b
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08772480B2

反応ノート

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