2-Aminoadamantane hydrochloride → 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide

HRID 12857

反応式

HRID 12857 の反応式
[C:1]([N:5]1[C:9]([Cl:10])=[C:8]([C:11]([OH:13])=O)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.Cl.[NH2:44][CH:45]1[CH:52]2[CH2:53][CH:48]3[CH2:49][CH:50]([CH2:54][CH:46]1[CH2:47]3)[CH2:51]2>ClCCl.CN(C=O)C.O>[CH:46]12[CH2:54][CH:50]3[CH2:49][CH:48]([CH2:53][CH:52]([CH2:51]3)[CH:45]1[NH:44][C:11]([C:8]1[CH:7]=[N:6][N:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:9]=1[Cl:10])=[O:13])[CH2:47]2

参加物

8

反応物 4

HCID 253312-Aminoadamantane hydrochlorideHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 534235531-(tert-Butyl)-5-chloro-1H-pyrazole-4-carboxylic acid2 回

生成物 1

HCID 250144171-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide収率 83%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

tert-Butyl-5-chloro-1H-pyrazole-4-carboxylic acid (Intermediate 9, 0.5 g, 2.47 mmol) was dissolved in a mixture of dry dichloromethane (12 mL) and dry DMF (3 mL). DIPEA (2.6 mL, 14.9 mmol) and TSTU (0.9 g, 2.7 mmol) were added to the above mixture. After the mixture was stirred for 1 h, the appearance of active ester was detected by LC-MS. Then 2-aminoadamantane hydrochloride (0.44 g, 2.34 mmol) was added. After another 2 hours water was added and the organic layer was separated. The aqueous layer was extracted twice with dichloromethane. The combined organic phases were dried under vacuum and purified by C-18 reverse phase preparative-HPLC with a gradient of 10-100% acetonitrile/water to give 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (650 mg, 83%). Mass spectrum: m/z: 336.2 (M+1).

後処理

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted twice with dichloromethane
  3. customThe combined organic phases were dried under vacuum
  4. custompurified by C-18 reverse phase preparative-HPLC with a gradient of 10-100% acetonitrile/water

出典と根拠

ORDレコード
ord-1e5a5975997648e3a2015a610cf55dc5
出典データセット
uspto-grants-2010_06
特許番号
US07728029B2

関連ノート

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