Acetic Acid → HCID 89922683、化合物

HRID 921849ノート

反応式

HRID 921849 の反応式
[Cl:1][C:2]1[C:7]([CH:8]([CH3:11])[CH:9]=O)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1.[NH:39]1[CH2:42][CH:41]([OH:43])[CH2:40]1.CC(O)=O.C([BH3-])#N.[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[C:7]([CH:8]([CH3:11])[CH2:9][N:39]2[CH2:42][CH:41]([OH:43])[CH2:40]2)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1

参加物

8

反応物 4

HCID 176Acetic AcidHCID 15142903-HydroxyazetidineHCID 5003444Sodium cyanoborohydrideHCID 89922524HCID 89922524、化合物

生成物 1

HCID 89922683HCID 89922683、化合物収率 63.7%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-((2-chloro-5-cyano-3-(1-oxopropan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (25 mg, 0.047 mmol) was taken up in THF (0.5 mL) and a solution of azetidin-3-ol (6.94 mg, 0.095 mmol) in MeOH (0.333 mL) was added. A drop of AcOH was added and the solution was stirred for 10 min. Next, sodium cyanoborohydride (5.96 mg, 0.095 mmol) was added and the reaction was stirred for 1 h. The reaction was diluted with EtOAc and washed with 2M K3PO4 solution. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-10% MeOHiDCM; 12 g column). 2-((2-chloro-5-cyano-3-(1-(3-hydroxyazetidin-1-yl)propan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (17.5 mg) was obtained as a yellow glass.

後処理

  1. stirringthe reaction was stirred for 1 h
  2. washwashed with 2M K3PO4 solution
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified by flash column chromatography (0-10% MeOHiDCM; 12 g column)

出典と根拠

ORDレコード
ord-e91af04dda534781924aade702c596f0
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…