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

HRID 1793192ノート

反応式

HRID 1793192 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

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) δ 9.15 (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/CI): 440.3 (M+H)+.

後処理

  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)

出典と根拠

ORDレコード
ord-12cb8a95f5ef4ea8885b99cd70a92718
出典データセット
uspto-grants-2006_07
特許番号
US07078529B2

反応ノート

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