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Isopropanol → 1-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)-3-(4-(2-methoxyethoxy)phenyl)urea

HRID 1812101
ノート
印刷プレビュー

反応式

HRID 1812101 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]([NH:33][C:34]5[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:36][CH:35]=5)=[O: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)([O-])[O-].[Na+].[Na+].CC(O)C>C(O)(C(F)(F)F)=O.C(Cl)(Cl)Cl>[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]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:36][CH:35]=4)=[O: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

7

反応物 4

HCID 3776IsopropanolHCID 10340Sodium CarbonateHCID 62406Trifluoromethanesulfonic acidHCID 666121101-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)-3-(4-(2-methoxyethoxy)phenyl)urea

生成物 1

HCID 595482811-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)-3-(4-(2-methoxyethoxy)phenyl)urea
収率 69.2%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
60 °C

実験手順

A solution of 1-(5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)-3-(4-(2-methoxyethoxy)phenyl)urea (0.176 g, 0.231 mmol) and trifluoromethanesulfonic acid (0.020 mL, 0.231 mmol) in TFA (2 mL) was stirred at rt for 30 min then warmed up to 60° C. and stirred overnight. After cooling to rt, solid sodium carbonate was added in portions until effervescence subsided. 25% iPrOH in CHCl3 (+1% NH4OH) was added to the residue, and the organic phase was washed with sodium bicarbonate. The material was not fully soluble in the organic layer so the organic layer containing solid was directly dried under vacuum (no drying agent was added). The crude product was purified by preparative HPLC using Phenomenex, Gemni 5 micron C18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 15 min). The fractions containing product were collected and concentrated in vacuo. Sodium bicarbonate was added and the resulting solid was collected to give 1-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-chloropyridin-2-ylamino)pyridin-2-yl)-3-(4-(2-methoxyethoxy)phenyl)urea (0.0834 g, 69% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.82 (br. s., 1H); 10.10 (br. s., 1H); 9.30 (br. s., 1H); 8.62-8.86 (m, 2H); 8.36 (d, J=2.54 Hz, 1H); 8.13 (br. s., 7.96 (br. s., 1H); 7.84 (br. s., 1H); 7.51 (br. s., 1H); 7.33-7.46 (m, 2H); 6.90 (d, J=8.41 Hz, 2H); 4.04 (br. s., 2H); 3.64 (d, J=3.72 Hz, 2H); 3.30 (d, J=5.87 Hz, 3H); 2.44 (d, J=5.48 Hz, 3H). m/z (ESI, +ve ion) 521.9 (M+H)+.

後処理

  1. temperatureAfter cooling to rt
  2. washthe organic phase was washed with sodium bicarbonate
  3. additioncontaining solid
  4. customwas directly dried under vacuum (no drying agent
  5. additionwas added)
  6. customThe crude product was purified by preparative HPLC
  7. customC18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 15 min)
  8. additionThe fractions containing product
  9. customwere collected
  10. concentrationconcentrated in vacuo
  11. additionSodium bicarbonate was added
  12. customthe resulting solid was collected

出典と根拠

ORDレコード
ord-467f25b8aa884aa2945f1b4f7cef3236
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08362241B2

反応ノート

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