Sodium Hydroxide → 6-Methyl-pyridine-2-carboxylic acid {3-[4-(2-naphthalen-1-yl-acetylamino)-imidazol-1-yl]-cyclobutyl}-amide

HRID 353921Notes

Reaction equation

HRID 353921 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.[NH2:23][C@@H:24]1[CH2:27][C@H:26]([N:28]2[CH:32]=[C:31]([NH:33][C:34](=[O:46])[CH2:35][C:36]3[C:45]4[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=4)[CH:39]=[CH:38][CH:37]=3)[N:30]=[CH:29]2)[CH2:25]1.[OH-].[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.O>[C:36]1([CH2:35][C:34]([NH:33][C:31]2[N:30]=[CH:29][N:28]([CH:26]3[CH2:27][CH:24]([NH:23][C:8]([C:6]4[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=4)=[O:10])[CH2:25]3)[CH:32]=2)=[O:46])[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:39]=[CH:38][CH:37]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 702826-Methylpyridine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178511735HCID 178511735, compound

Product 1

HCID 101141106-Methyl-pyridine-2-carboxylic acid {3-[4-(2-naphthalen-1-yl-acetylamino)-imidazol-1-yl]-cyclobutyl}-amideYield 98.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 6-methylpicolinic acid (9.4 mg, 0.07 mmol) in methylene chloride was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (84 mg) and DMAP (2 mg) at 23° C. After stirring for 10 min, N-[1-(cis-3-amino-cyclobutyl)-1H-imidazol-4-yl]-2-naphthalen-1-yl-acetamide (Example 6, 20 mg, 0.06 mmol), was added. The resulting mixture was then stirred for 3 h. Water was added, the solution was made neutral with aqueous NaOH and was extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography (20:1 CHCl3—MeOH) gave 26 mg (95% yield) of 6-methyl-pyridine-2-carboxylic acid {3-[4-(2-naphthalen-1-yl-acetylamino)-imidazol-1-yl]-cyclobutyl}-amide; 1H NMR (400 MHz, CDCl3) δ9.15 (s, 1H), 8.28 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.5 Hz, 1H), 7.96 (d, J=7.5 Hz, 1H), 7.97 (d, J=7.5 Hz, 1H), 7.81 (dd, J=2.4, 6.6 Hz, 1H), 7.72 (m, 1H), 7.5 (m, 5H), 7.2 (m, 1H), 7.16 (s, 1H), 4.45 (m, 1H), 4.25 (m, 1H), 4.18 (s, 2H), 2.98 (m, 2H), 2.60 (s, 3H), 2.40 (m, 2H); MS (AP/Cl): 440.3 (M+H)+.

Workup

  1. stirringThe resulting mixture was then stirred for 3 h
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (20:1 CHCl3—MeOH)

Sources & evidence

ORD record
ord-dbb57b4f1bb649c181cbd34fe86ef603
Source dataset
uspto-grants-2004_06
Patent number
US06756385B2

Reaction notes

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