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

HRID 12857

Reaction equation

HRID 12857 reaction equation
[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

Participants

8

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1e5a5975997648e3a2015a610cf55dc5
Source dataset
uspto-grants-2010_06
Patent number
US07728029B2

Linked notes

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