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

HRID 12832

Reaction equation

HRID 12832 reaction equation
[C:1]([N:5]1[C:9]([C:10]([F:13])([F:12])[F:11])=[C:8]([C:14]([OH:16])=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.[NH2:47][CH:48]1[CH:55]2[CH2:56][CH:51]3[CH2:52][CH:53]([CH2:57][CH:49]1[CH2:50]3)[CH2:54]2>ClCCl.CN(C=O)C.O>[CH:49]12[CH2:57][CH:53]3[CH2:52][CH:51]([CH2:56][CH:55]([CH2:54]3)[CH:48]1[NH:47][C:14]([C:8]1[CH:7]=[N:6][N:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:9]=1[C:10]([F:11])([F:12])[F:13])=[O:16])[CH2:50]2

Participants

8

Reactant 4

HCID 253312-Aminoadamantane hydrochlorideHCID 81531DiisopropylethylamineHCID 14820391-tert-Butyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid2×HCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate

Product 1

HCID 250135441-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamideYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (Intermediate 7, 61 mg, 0.26 mmol) was dissolved in a mixture of dry dichloromethane (3.2 mL) and dry DMF (0.8 mL). DIPEA (0.23 mL, 1.3 mmol) and TSTU (93 mg, 0.28 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 (58 mg, 0.31 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 C-18 reversed phase HPLC with a gradient of 10-100% acetonitrile/water to give 1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid adamantan-2-ylamide (62 mg, 65%). Mass spectrum: m/z: 370.2 (M+1).

Workup

  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 C-18

Sources & evidence

ORD record
ord-d53e24288b474cab86af0923b73f4cca
Source dataset
uspto-grants-2010_06
Patent number
US07728029B2

Linked notes

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