1-Adamantaneacetic acid → 4-(2-Adamantan-1-ylacetylamino)pyrazolo[1,5-a]pyridine-2-carboxylic acid ethyl ester

HRID 2039785Notes

Reaction equation

HRID 2039785 reaction equation
[C:1]12([CH2:11][C:12](O)=[O:13])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:15]([O:17][C:18]([C:20]1[CH:29]=[C:23]2[C:24]([NH2:28])=[CH:25][CH:26]=[CH:27][N:22]2[N:21]=1)=[O:19])[CH3:16].[Cl-].ClC1N(C)CC[NH+]1C.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.C(#N)C.C(N(CC)CC)C>[CH2:15]([O:17][C:18]([C:20]1[CH:29]=[C:23]2[C:24]([NH:28][C:12](=[O:13])[CH2:11][C:1]34[CH2:10][CH:5]5[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]5)[CH2:8]3)[CH2:2]4)=[CH:25][CH:26]=[CH:27][N:22]2[N:21]=1)=[O:19])[CH3:16]

Participants

9

Reactant 4

HCID 1232211-Adamantaneacetic acidHCID 516892Sodium BicarbonateHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 595390024-Aminopyrazolo[1,5-a]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 250951064-(2-Adamantan-1-ylacetylamino)pyrazolo[1,5-a]pyridine-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A 1.0 M solution of triethylamine in toluene (0.3 mL) is added to a solution of 1-adamantaneacetic acid (14 mg, 80 μmol) and 4-aminopyrazolo[1,5-a]pyridine-2-carboxylic acid ethyl ester (12 mg, 60 μmol) in DMF (0.3 mL) under N2. A solution of 2-chloro-1,3-dimethylimidazolinium chloride (20 mg, 120 μmol) in ACN (0.3 mL) is added. The reaction vessel is sealed and the mixture is warmed to 50° C. for 2 h. The mixture is cooled to rt. 50% Sat. aq. NaHCO3 (2 mL) is added. The solution is extracted with Et OAc (2×1 mL). The combined organics are concentrated. Purification by preparative thin layer chromatography (2:1 hexanes:EtOAc) affords the title compound as a light tan solid. 1H NMR (400 MHz, CDCl3) δ: 8.32 (d, 1H), 8.05 (d, 1H), 7.15 (s, 1H), 7.05 (s, 1H), 6.91 (t, 1H), 4.59 (q, 2H), 2.21 (s, 2H), 1.98-2.06 (m, 3H), 1.56-1.78 (m, 12H), 1.46 (t, 3H). LC-MS m/z (M+H+): 382.10.

Workup

  1. customThe reaction vessel is sealed
  2. temperatureThe mixture is cooled to rt
  3. extractionThe solution is extracted with Et OAc (2×1 mL)
  4. concentrationThe combined organics are concentrated
  5. customPurification by preparative thin layer chromatography (2:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-ed7c0bdd9c2e484eb066882092b0e561
Source dataset
uspto-grants-2013_11
Patent number
US08580812B2

Reaction notes

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