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

HRID 220592노트

반응식

HRID 220592 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 16217500bis[(diphenylphosphanyl)methyl]-amine palladium (II) dichloride촉매HCID 702Ethanol용매HCID 887Methanol용매2회

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온도
140 °C

실험 절차

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]).

후처리

  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.

출처 및 근거

ORD 기록
ord-c9595486ffde4647bd7a32b6b61e8aac
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202873B2

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