Acetic Acid → 2-((2-Chloro-5-cyano-3-(1-methylpiperidin-4-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921663ノート

反応式

HRID 921663 の反応式
[C:1](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[C:21]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:20][C:19]([C:28]#[N:29])=[CH:18][C:17]=1[NH:30][C:31]1[N:36]=[C:35]([N:37]([CH:47]2[CH2:49][CH2:48]2)CC2C=CC(OC)=CC=2)[C:34]2=[N:50][CH:51]=[C:52]([C:53]#[N:54])[N:33]2[N:32]=1.C=O.O.CC(O)=O.C([O-])(O)=O.[Na+].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:15][C:16]1[C:21]([CH:22]2[CH2:23][CH2:24][N:25]([CH3:1])[CH2:26][CH2:27]2)=[CH:20][C:19]([C:28]#[N:29])=[CH:18][C:17]=1[NH:30][C:31]1[N:36]=[C:35]([NH:37][CH:47]2[CH2:49][CH2:48]2)[C:34]2=[N:50][CH:51]=[C:52]([C:53]#[N:54])[N:33]2[N:32]=1

参加物

10

反応物 8

HCID 176Acetic AcidHCID 712FormaldehydeHCID 962WaterHCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 867085292-((2-Chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

生成物 1

HCID 867085282-((2-Chloro-5-cyano-3-(1-methylpiperidin-4-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile収率 87.5%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
50 °C

実験手順

Sodium triacetoxyborohydride (24.10 mg, 0.114 mmol) was added to a stirred suspension of 2-((2-chloro-5-cyano-3-(piperidin-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (30.0 mg, 0.038 mmol), formaldehyde 37% in water (8.47 μL, 0.114 mmol) and HOAc (16.27 μL, 0.190 mmol) in DCE (379 μL) at room temperature for 30 min. Sat. aq. NaHCO3 solution was slowly added (gas evolution) and the reaction was left stirring for 10 min. It was extracted with DCM. The organic phase was dried with sodium sulfate and the solvents were removed. The crude intermediate was dissolved in DCE (1 mL) and anisole (20.70 μL, 0.190 mmol), and TFA (0.5 mL) were added. The resulting mixture was heated at 50° C. for 3 h. Removal of the solvents was followed by preparative HPLC (Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 methanol: water with 20-mM ammonium acetate; Gradient: 40-80% B over 20 minutes, then a 5-minute hold at 100%. B; Flow: 20 mL/min.). Fractions containing the desired product were combined and dried via centrifugal evaporation to afford 14.9 mg of 2-((2-chloro-5-cyano-3-(1-methylpiperidin-4-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile.

後処理

  1. waitthe reaction was left
  2. extractionIt was extracted with DCM
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. customthe solvents were removed
  5. dissolutionThe crude intermediate was dissolved in DCE (1 mL)
  6. customRemoval of the solvents
  7. waitGradient: 40-80% B over 20 minutes
  8. customa 5-minute hold
  9. additionFractions containing the desired product
  10. customdried via centrifugal evaporation

出典と根拠

ORDレコード
ord-e8c99da390ba4adab0c4f0a87b3f38de
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

反応ノート

読み込み中…