Diisopropylethylamine → 1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide

HRID 12836

Reaktionsgleichung

Reaktionsgleichung von HRID 12836
[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.[NH2:45][CH:46]1[CH:53]2[CH2:54][C:49]3([OH:56])[CH2:50][CH:51]([CH2:55][CH:47]1[CH2:48]3)[CH2:52]2>ClCCl.CN(C=O)C.O>[OH:56][C:49]12[CH2:54][CH:53]3[CH2:52][CH:51]([CH2:55][CH:47]([CH:46]3[NH:45][C:13]([C:7]3[CH:6]=[N:5][N:4]([CH:1]4[CH2:2][CH2:3]4)[C:8]=3[C:9]([F:10])([F:11])[F:12])=[O:15])[CH2:48]1)[CH2:50]2

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 28574474-Aminoadamantan-1-olHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 589728211-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid2×

Produkt 1

HCID 250138571-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-Cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (Intermediate 6, 100 mg, 0.45 mmol) was dissolved in a mixture of dry dichloromethane (4 mL) and dry DMF (1 mL). DIPEA (0.5 mL, 2.9 mmol) and TSTU (165 mg, 0.5 mmol) were added to the above mixture. After the mixture was stirred for 2 h, the appearance of active ester was detected by LC-MS. Then 4-amino-adamantan-1-ol (77 mg, 0.46 mmol) was added. After another 4 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. The crude mixture was purified by C-18 reversed phase preparative-HPLC with a gradient of 10-100% acetonitrile/water to give 1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide (79 mg, 48%. Mass spectrum: m/z: 370.2 (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. customThe crude mixture was purified by C-18

Quellen und Nachweise

ORD-Eintrag
ord-1d5669c1dacf4500b4f798b19027bbba
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07728029B2

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