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

HRID 553508Notes

Reaction equation

HRID 553508 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
70 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-ecb647bb7eab4b8e8f10ca04e1d0a1c1
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

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