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

HRID 220585ノート

反応式

HRID 220585 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]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[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+].[C:33]([NH:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1)(=[O:35])[CH3:34].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].[CH3:20][C:19]1[N:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:17]=[CH:16][C:15]=1[CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:3]2[C:2]([C:41]3[CH:42]=[CH:43][C:38]([CH2:37][NH:36][C:33](=[O:35])[CH3:34])=[CH:39][CH:40]=3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:9][CH2:10]1

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 223094544-[(Acetylamino)methyl]benzeneboronic acidHCID 866416633'-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

生成物 1

HCID 68594807N-{4-[4-(5-Methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochloride収率 96%

試薬・触媒・溶媒 2

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

実験手順

Combine 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.290 g, 0.786 mmol), potassium carbonate (0.261 g, 1.89 mmol), (4-acetamidomethylphenyl)boronic acid (0.182 g, 0.943 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.009 g, 0.008 mmol) in N,N-dimethylacetamide (1.6 mL). Add water (790 μL), and reflux reaction for 18 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 (365 mg, 96%). Dissolve the free base (0.363 g, 0.754 mmol) in acetonitrile (904 μL) and add aq. 1 N HCl solution (904 μL, 0.904 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (392 mg, 100%). MS (ES): m/z=482 [M+H]+.

後処理

  1. customreaction for 18 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-dd379698ce2e4cfd948a536552620e84
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…