反応式
Cl.Cl[C:3]1[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:17]=[N:18][N:19]([CH3:22])[C:20]=3[CH3:21])[CH2:11][CH2:10]2)=[N:5][CH:6]=[CH:7][N:8]=1.[C:23]([NH:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)(=[O:25])[CH3:24].C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][N:19]1[C:20]([CH3:21])=[C:16]([CH2:15][N:12]2[CH2:13][CH2:14][N:9]([C:4]3[C:3]([C:30]4[CH:31]=[CH:32][C:27]([NH:26][C:23](=[O:25])[CH3:24])=[CH:28][CH:29]=4)=[N:8][CH:7]=[CH:6][N:5]=3)[CH2:10][CH2:11]2)[CH:17]=[N:18]1参加物
反応物 3
生成物 1
試薬・触媒・溶媒 3
反応条件
- 温度
- 90 °C
実験手順
Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl hydrochloride salt (0.5 g, 1.63 mmol) in N,N-dimethylacetamide (5 mL) and water (2 mL). Add 4-acetamidophenylboronic acid (1.2 eq., 0.35 g, 1.96 mmol). Add tetrakis(triphenylphosphine)palladium(0) (0.01 eq., 0.019 g, 0.016 mmol). Add potassium carbonate (3.6 eq., 0.54 g, 3.9 mmol). Heat at 90° C. for 10 hr. Purify by normal phase chromatography with 6% 7N ammonia-methanol/ethyl acetate to give N-{4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-acetamide (0.25 g, 38%). MS (ES): m/z=406.2[M+H]. Dissolve this free base (0.25 g, 0.6 mmol) in acetonitrile (1 mL) and water (4 mL). Add aq. 1 N HCl (1 eq., 0.60 mmol, 0.60 mL). Freeze the solution to −78° C. in a dry-ice/acetone bath. Place the solution in the lyophilize for 48 hr. to give the title compound salt (0.26 g, 99%). MS (ES): m/z=406.2[M+H].
後処理
- customPurify by normal phase chromatography with 6% 7N ammonia-methanol/ethyl acetate
出典と根拠
- ORDレコード
- ord-533ffe1c331943cc9bea70a7aa54b67a
- 出典データセット
- uspto-grants-2012_06
- 特許番号
- US08202873B2
関連ノート
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