Sodium Carbonate → methyl 4-(3-(4-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)pyrazin-2-yl)benzoate

HRID 220592ノート

反応式

HRID 220592 の反応式
Cl[C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=3)[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[CH3:22][O:23][C:24]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)=[O:25].C(=O)([O-])[O-].[Na+].[Na+].Cl.CN1C(C)=C(CN2CCN(C3C(C4C=CC(C(OC)C)=CC=4)=NC=CN=3)CC2)C=N1>[Pd](Cl)Cl.C1(P(CNCP(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO.C(O)C>[CH3:20][N:18]1[CH:19]=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:29]4[CH:30]=[CH:31][C:26]([C:24]([O:23][CH3:22])=[O:25])=[CH:27][CH:28]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[C:16]([CH3:21])=[N:17]1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 866416563'-Chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazineHCID 866416674-(1,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3'-[4-(1-methoxy-ethyl)-phenyl]-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl hydrochloride

生成物 1

HCID 59321827methyl 4-(3-(4-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)pyrazin-2-yl)benzoate収率 26%

試薬・触媒・溶媒 3

HCID 16217500bis[(diphenylphosphanyl)methyl]-amine palladium (II) dichloride触媒HCID 702Ethanol溶媒HCID 887Methanol溶媒2 回

反応条件

温度
140 °C

実験手順

Charge a microwave tube with 3′-chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.150 g, 0.490 mmoles), bis[(diphenylphosphanyl)methyl]-amine palladium (II) dichloride polymer bound (0.061 g, 0.049 mmoles, 0.1 eq), 4-(methoxycarbonyl)phenylboronic acid (0.176 g, 0.98 mmoles, 2 eq), sodium carbonate (0.192 g, 1.8 mmoles, 3.7 eq) and 3 ml of ethanol. Seal the reaction and heat under microwave conditions at 140° C. for 30 min. Cool down reaction and apply crude material to an SCX column prewashed with 10 ml methanol. Wash material with 10 ml of methanol, and release the product with 20 ml of a 2 N-ammonia/methanol solution. Purify the crude brown oil by reverse phase chromatography (28% isocratic acetonitrile/0.01 M ammonium bicarbonate in water, 80 ml/min., for 8 min., on a 30×75 mm, C18 Xterra column) to provide methyl 4-(3-(4-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)pyrazin-2-yl)benzoate as a white solid (0.051 g, 26% yield, ES+(m/z) 407 [M+H]). Convert the purified material to the hydrochloride salt by stirring a solution of the free base (0.045 g, 0.294 mmoles) in acetonitrile (5 ml) at room temperature and add 1 N HCl in water (0.294 ml, 0.294 mmoles) to give a yellow solution. After 5 min., freeze the solution and lyophilize to give the title compound as a white solid (0.056 g, 100% yield, ES+(m/z) 407 [M+H]).

後処理

  1. customSeal
  2. customthe reaction
  3. temperatureCool down reaction and apply crude material to an SCX column
  4. customPurify the crude brown oil by reverse phase chromatography (28% isocratic acetonitrile/0.01 M ammonium bicarbonate in water, 80 ml/min.

出典と根拠

ORDレコード
ord-c9595486ffde4647bd7a32b6b61e8aac
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

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