Water → N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-methanesulfonamide hydrochloride

HRID 220583ノート

反応式

HRID 220583 の反応式
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([CH2:21][CH3:22])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][S:30]([NH:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)(=[O:32])=[O:31].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].[CH2:21]([N:18]1[C:19]([CH3:20])=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:38]4[CH:39]=[CH:40][C:35]([CH2:34][NH:33][S:30]([CH3:29])(=[O:31])=[O:32])=[CH:36][CH:37]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1)[CH3:22]

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 22309452[4-(Methanesulfonamidomethyl)phenyl]boronic acid2 回HCID 866416643'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

生成物 1

HCID 68597904N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-methanesulfonamide hydrochloride収率 85%

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 3′-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.300 g, 0.935 mmol), potassium carbonate (0.310 g, 2.24 mmol), (4-methanesulfonylaminomethylphenyl)boronic acid (0.257 g, 1.12 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.009 mmol) in N,N-dimethylacetamide (1.9 mL). Add water (940 μL), and reflux reaction for 6 hr. Continue to heat at 70° C. for 18 hr. Add (4-methanesulfonylaminomethylphenyl) boronic acid (0.129 g, 0.56 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.009 mmol) and heat to 115° C. for 6 hr. Continue to stir at ambient temperature over 72 hr. Add DCM and wash with water. Extract water layer three times with DCM. Dry combined organics (magnesium sulfate) and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 to 20:80 methanol:ethyl acetate), to give the free base of the title compound (371 mg, 85%). Dissolve the free base (0.367 g, 0.781 mmol) in acetonitrile (938 μL) and add aq. 1 N HCl solution (938 μL, 0.938 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (397 mg, 100%). MS (ES): m/z=470 [M+H]+.

後処理

  1. customreaction for 6 hr
  2. washAdd DCM and wash with water
  3. customDry
  4. custompurify (silica gel chromatography
  5. washeluting with 50:50 to 100:0 ethyl acetate

出典と根拠

ORDレコード
ord-b6bb829bc2f64100a150fd5b3806118f
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

読み込み中…