2-Aminoadamantane hydrochloride → 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide

HRID 12833

반응식

HRID 12833 반응식
[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[C:3]=1[C:12]([OH:14])=O.CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.Cl.[NH2:45][CH:46]1[CH:53]2[CH2:54][CH:49]3[CH2:50][CH:51]([CH2:55][CH:47]1[CH2:48]3)[CH2:52]2>ClCCl.CN(C=O)C.O>[CH:47]12[CH2:55][CH:51]3[CH2:50][CH:49]([CH2:54][CH:53]([CH2:52]3)[CH:46]1[NH:45][C:12]([C:3]1[C:4]([C:8]([F:11])([F:10])[F:9])=[N:5][N:6]([CH3:7])[C:2]=1[Cl:1])=[O:14])[CH2:48]2

참가 물질

8

반응물 4

HCID 253312-Aminoadamantane hydrochlorideHCID 81531DiisopropylethylamineHCID 27738065-Chloro-1-Methyl-3-(Trifluoromethyl)-1H-Pyrazole-4-Carboxylic AcidHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate

생성물 1

HCID 250135465-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide수율 38%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

5-Chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (91 mg, 0.4 mmol, CAS#: 128455-63-0, purchased from Maybridge) was dissolved in a mixture of dry dichloromethane (3.2 mL) and dry DMF (0.8 mL). DIPEA (0.28 mL, 1.6 mmol) and TSTU (145 mg, 0.44 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 (75 mg, 0.4 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 reversed phase HPLC with a gradient of 10-100% acetonitrile/water to give 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (55 mg, 38%). Mass spectrum: m/z: 362.1 (M+1).

후처리

  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

출처 및 근거

ORD 기록
ord-568874b6af5e4e4ea6e75104603ebf6e
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728029B2

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