Methanesulfonic Acid → Edoxaban

HRID 707489ノート

反応式

HRID 707489 の反応式
CS(O)(=O)=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([NH:13][C:14](=[O:37])[C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])[CH2:20][C@H:19]2[NH:29][C:30](=O)[O:31]C(C)(C)C)=[O:16])=[N:11][CH:12]=1.Cl.[CH3:39][N:40]1[CH2:45][CH2:44][C:43]2[N:46]=[C:47](C(O)=O)[S:48][C:42]=2[CH2:41]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(#N)C.O.C(N(CC)CC)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([NH:13][C:14](=[O:37])[C:15]([NH:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([C:24]([N:26]([CH3:27])[CH3:28])=[O:25])[CH2:20][C@H:19]2[NH:29][C:30]([C:47]2[S:48][C:42]3[CH2:41][N:40]([CH3:39])[CH2:45][CH2:44][C:43]=3[N:46]=2)=[O:31])=[O:16])=[N:11][CH:12]=1

参加物

9

反応物 5

HCID 6395Methanesulfonic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 111490315-Methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-carboxylic acid--hydrogen chloride (1/1)HCID 46911214EthanediaMide iMpurity D

生成物 1

HCID 10280735Edoxaban収率 92.7%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒2 回

実験手順

Methanesulfonic acid (66 ml) was added to a suspension of tert-butyl [(1R,2S,5S)-2-({[(5-chloropyridin-2-yl)amino](oxo)acetyl}amino)-5-(dimethylaminocarbonyl)cyclohexyl]carbamate (8) (95.1 g) in acetonitrile (1900 ml) at room temperature, and the mixture was stirred at this temperature for 2 hours. To the reaction solution, triethylamine (155 ml), 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-carboxylic acid hydrochloride (10) (52.5 g), 1-hydroxybenzotriazole (33.0 g), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (46.8 g) were added under ice cooling, and the mixture was stirred at room temperature for 16 hours. Triethylamine and water were added thereto, and the mixture was stirred for 1 hour under ice cooling. Then, crystals were collected by filtration to obtain the title compound (A) (103.2 g).

後処理

  1. stirringthe mixture was stirred at room temperature for 16 hours
  2. stirringthe mixture was stirred for 1 hour under ice cooling
  3. filtrationThen, crystals were collected by filtration

出典と根拠

ORDレコード
ord-539846edb53f498ab2d0cd1cb53cfe60
出典データセット
uspto-grants-2015_11
特許番号
US09175012B2

反応ノート

読み込み中…