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

HRID 921765

反応式

HRID 921765 の反応式
[Cl:1][C:2]1[C:7]([CH:8]=O)=[CH:6][C:5]([C:10]#[N:11])=[CH:4][C:3]=1[NH:12][C:13]1[N:18]=[C:17]([NH:19][CH:20]2[CH2:22][CH2:21]2)[C:16]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:15]2[N:14]=1.[CH3:28][S:29]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)(=[O:31])=[O:30].COC(OC)OC.C(O)(=O)C.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl.C1COCC1>[Cl:1][C:2]1[C:7]([CH2:8][N:35]2[CH2:36][CH2:37][N:32]([S:29]([CH3:28])(=[O:31])=[O:30])[CH2:33][CH2:34]2)=[CH:6][C:5]([C:10]#[N:11])=[CH:4][C:3]=1[NH:12][C:13]1[N:18]=[C:17]([NH:19][CH:20]2[CH2:22][CH2:21]2)[C:16]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:15]2[N:14]=1

参加物

10

反応物 6

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 516892Sodium BicarbonateHCID 7091611-(Methylsulfonyl)piperazineHCID 5003444Sodium cyanoborohydride2 回HCID 867086482-((2-Chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

生成物 1

HCID 867086502-((2-Chloro-5-cyano-3-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile収率 31.2%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 2-((2-chloro-5-cyano-3-formylphenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 400) (18 mg, 0.048 mmol), 1-(methylsulfonyl)piperazine (9.5 mg, 0.058 mmol), trimethylorthoformate (0.027 mL, 0.242 mmol), and acetic acid (3 μL, 0.05 mmol) in a mixture of MeOH (0.5 mL) and DCM (0.5 mL) was stirred at room temperature for 15 min. A solution of sodium cyanoborohydride (0.097 mL, 1M in THF mL, 0.097 mmol) was added and the reaction was left stirring at room temperature overnight. Additional sodium cyanoborohydride (0.097 mL, 1M in THF mL, 0.097 mmol) was added and the reaction was left stirring for 1 day. A saturated aq. solution of NaHCO3 solution was added and, after 15 min, this was extracted with a mixture of 5% MeOH in DCM (5×). The combined organic extracts were dried with sodium sulfate and the solvent was removed. Silica gel radial chromatography of the residue eluting with DCM containing 0 to 2% MeOH afforded the title compound (7.9 mg) as foam.

後処理

  1. waitthe reaction was left
  2. stirringstirring at room temperature overnight
  3. waitthe reaction was left
  4. stirringstirring for 1 day
  5. extractionthis was extracted with a mixture of 5% MeOH in DCM (5×)
  6. dry with materialThe combined organic extracts were dried with sodium sulfate
  7. customthe solvent was removed
  8. washSilica gel radial chromatography of the residue eluting with DCM containing 0 to 2% MeOH

出典と根拠

ORDレコード
ord-8e08c63474f046728e9f5eb23e60a56d
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

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