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Water → N-{2-[3'-(4-Hydroxymethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-N-methyl-benzenesulfonamide hydrochloride

HRID 553508
ノート
印刷プレビュー

反応式

HRID 553508 の反応式
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[OH:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.O>CN(C)C(=O)C.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>[ClH:1].[OH:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)(=[O:19])=[O:18])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:37][CH:36]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acid2 回HCID 86640201N-[2-(3'-Chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-N-methyl-benzenesulfonamide

生成物 1

HCID 67366776N-{2-[3'-(4-Hydroxymethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-N-methyl-benzenesulfonamide hydrochloride
収率 78%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒2 回HCID 31374Dimethylacetamide溶媒

反応条件

温度
70 °C

実験手順

Combine N-[2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-N-methyl-benzenesulfonamide (0.300 g, 0.758 mmol), potassium carbonate (0.251 g, 1.82 mmol), (4-(hydroxymethyl)phenyl boronic acid (0.138 g, 0.909 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) in N,N-dimethylacetamide (1.5 mL). Add water (760 μL), and reflux reaction for 6 hr. Continue to heat at 70° C. for 18 hr. Add (4-(hydroxymethyl)phenyl boronic acid (0.069 g, 0.56 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) and heat to 115° C. for 6 hr. Continue to stir at ambient temperature over 72 hr. Add dichloromethane and wash with water. Extract the aqueous layer three times with dichloromethane. Dry the combined organic layers and purify (silica gel chromatography, eluting with 0:100 to 100:0 ethyl acetate:hexanes), to give the free base of the title compound (278 mg, 78%).

後処理

  1. customreaction for 6 hr
  2. temperatureheat to 115° C. for 6 hr
  3. washAdd dichloromethane and wash with water
  4. extractionExtract the aqueous layer three times with dichloromethane
  5. customDry the combined organic layers
  6. custompurify
  7. wash(silica gel chromatography, eluting with 0:100 to 100:0 ethyl acetate:hexanes)

出典と根拠

ORDレコード
ord-ecb647bb7eab4b8e8f10ca04e1d0a1c1
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08048884B2

反応ノート

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