Dimethyl Sulfoxide → tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

HRID 1050562ノート

反応式

HRID 1050562 の反応式
[C:1]([C:3]1[N:4]=[CH:5][C:6]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@H:28]2[CH3:41])=[N:7][C:8]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)#[N:2].CS(C)=[O:44].OO.[OH-].[Na+]>CO.CC#N>[C:1]([C:3]1[N:4]=[CH:5][C:6]([N:27]2[CH2:32][CH2:31][CH2:30][C@@H:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[C@H:28]2[CH3:41])=[N:7][C:8]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)(=[O:44])[NH2:2]

参加物

7

反応物 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen Peroxide2 回HCID 14798Sodium Hydroxide2 回HCID 118136128tert-butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate

生成物 1

HCID 118136127tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate収率 97%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
0 °C

実験手順

tert-Butyl (2R,3R)-1-(5-cyano-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (312) (430 mg, 0.74 mmol) was dissolved in MeOH (25 mL), DMSO (4.4 mL), and TEA (0.22 mL, 1.6 mmol). The solution was cooled to 0° C., and a pre-mixed solution of 30% H2O2 (175 μL, 1.5 mmol) and 4N NaOH (384 μL, 1.5 mmol) was added. The reaction was stirred for 1 hour at 0° C. An additional amount of the pre-mixed solution 30% H2O2 (175 μL, 1.5 mmol) and 4N NaOH (384 μL, 1.5 mmol) was added, and the reaction was stirred for an additional hour at 0° C. MeCN (10 mL) was then added and the solution was stirred for 10 minutes at room temperature. The solvents were removed under reduced pressure, and the residue was subjected to silica flash column chromatography (MeOH/DCM) to give tert-butyl (2R,3R)-1-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (313) (430 mg, 0.74 mmol, 97% yield).

後処理

  1. stirringthe reaction was stirred for an additional hour at 0° C
  2. stirringthe solution was stirred for 10 minutes at room temperature
  3. customThe solvents were removed under reduced pressure

出典と根拠

ORDレコード
ord-e8e8c6c753394bf9afc318ff4ddefb59
出典データセット
uspto-grants-2016_07
特許番号
US09382246B2

反応ノート

読み込み中…