反応式
CC1C(CN2C=C(C(N=[N+]=[N-])=O)C=N2)=C(C)ON=1.[N:19]([C:22]1[CH:23]=[N:24][N:25]([CH2:27][C:28]2[C:29]([CH3:34])=[N:30][O:31][C:32]=2[CH3:33])[CH:26]=1)=[C:20]=[O:21].Cl.[NH2:36][C:37]([CH3:44])([CH3:43])[C:38](OCC)=[O:39]>C1(C)C=CC=CC=1>[CH3:34][C:29]1[C:28]([CH2:27][N:25]2[CH:26]=[C:22]([N:19]3[C:38](=[O:39])[C:37]([CH3:44])([CH3:43])[NH:36][C:20]3=[O:21])[CH:23]=[N:24]2)=[C:32]([CH3:33])[O:31][N:30]=1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- 50 °C
実験手順
1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide (Example 10-1a) (10 g, 41.0 mmol) is stirred under nitrogen in dry toluene (150 mL) along with molecular sieves at reflux until no emission of nitrogen was observed, which indicates complete conversion of 1-((3,5-dimethylisoxazol-4-yl) methyl)-1H-pyrazole-4-carbonyl azide into 4-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole. The solution was cooled down to 50° C. and ethyl 2-amino-2-methylpropanoate hydrochloride (5.30 g, 41.0 mmol) was added in one portion. Stirring continued for 3 hours at 50° C. followed by reflux for 12 hours. The mixture was filtered over a pad of celite. The filtrate was concentrated on the rotovap and the residue was purified over silica gel using 25% ethyl acetate in hexanes. Yield 65% (8.00 g), white solid. 1H NMR (DMSO-d6, 400 MHz): □s, 6H), 2.15 (s, 3H), 2.41 (s, 3H), 5.18 (s, 2H), 7.78 (d, J=0.4 Hz, 1H), 8.16 (d, J=0.4 Hz, 1H), 8.59 (br s, 1H). MS 304 (MH+). This compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 2.27 μM.
後処理
- temperatureat reflux until no emission of nitrogen
- temperatureby reflux for 12 hours
- filtrationThe mixture was filtered over a pad of celite
- concentrationThe filtrate was concentrated on the rotovap
- customthe residue was purified over silica gel using 25% ethyl acetate in hexanes
出典と根拠
- ORDレコード
- ord-6236a0ffadf94fda8f740651fd2c1960
- 出典データセット
- uspto-grants-2011_12
- 特許番号
- US08076491B2
関連ノート
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