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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
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HRID 553508 반응식
[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
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7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acid2회HCID 86640201N-[2-(3'-Chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-N-methyl-benzenesulfonamide

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매2회HCID 31374Dimethylacetamide용매

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온도
70 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-ecb647bb7eab4b8e8f10ca04e1d0a1c1
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08048884B2

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