2-Aminoadamantane hydrochloride → 1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide

HRID 12835

Reaktionsgleichung

Reaktionsgleichung von HRID 12835
[CH:1]1([N:4]2[C:8]([C:9]([F:12])([F:11])[F:10])=[C:7]([C:13]([OH:15])=O)[CH:6]=[N:5]2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.Cl.[NH2:46][CH:47]1[CH:54]2[CH2:55][CH:50]3[CH2:51][CH:52]([CH2:56][CH:48]1[CH2:49]3)[CH2:53]2>ClCCl.CN(C=O)C.O>[CH:48]12[CH2:56][CH:52]3[CH2:51][CH:50]([CH2:55][CH:54]([CH2:53]3)[CH:47]1[NH:46][C:13]([C:7]1[CH:6]=[N:5][N:4]([CH:1]3[CH2:2][CH2:3]3)[C:8]=1[C:9]([F:10])([F:11])[F:12])=[O:15])[CH2:49]2

Komponenten

8

Edukt 4

HCID 253312-Aminoadamantane hydrochlorideHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 589728211-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid2×

Produkt 1

HCID 250135481-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamideAusbeute 56,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-Cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (Intermediate 6, 20 mg, 0.09 mmol) was dissolved in a mixture of dry dichloromethane (1.6 mL) and dry DMF (0.2 mL). DIPEA (0.1 mL, 0.57 mmol) and TSTU (33 mg, 0.11 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 (17 mg, 0.09 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 layers were dried under vacuum and purified by silica chromatography eluting with a gradient of 0-40% ethyl acetate/hexanes, then 40% ethyl acetate/hexanes to give 1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (18 mg, 56%). Mass spectrum: m/z: 354.2 (M+1).

Aufarbeitung

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted twice with dichloromethane
  3. customThe combined organic layers were dried under vacuum
  4. custompurified by silica chromatography
  5. washeluting with a gradient of 0-40% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-4f6a0d022ce842589a91c7fec504bf5e
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728029B2

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