Potassium Iodide → 4-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

HRID 220536ノート

反応式

HRID 220536 の反応式
Cl.Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[N:12][CH:13]=[CH:14][N:15]=2)=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:31][CH2:32][C:33]1[C:34]([CH3:39])=[N:35][NH:36][C:37]=1[CH3:38]>C(#N)C>[CH3:39][C:34]1[C:33]([CH2:32][CH2:31][N:19]2[CH2:18][CH2:17][N:16]([C:11]3[C:10]([C:7]4[CH:8]=[CH:9][C:4]([F:3])=[CH:5][CH:6]=4)=[N:15][CH:14]=[CH:13][N:12]=3)[CH2:21][CH2:20]2)=[C:37]([CH3:38])[NH:36][N:35]=1

参加物

6

反応物 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5728794-(2-Bromoethyl)-3,5-dimethyl-1H-pyrazoleHCID 673669583'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl dihydrochloride

生成物 1

HCID 593218964-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3'-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl収率 0.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

Dissolve 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl dihydrochloride (0.200 g, 0.604 mmol) in acetonitrile (12 mL). Add potassium carbonate (0.334 g, 2.415 mmol), potassium iodide (0.005 g, 0.030 mmol), and 4-(2-bromo-ethyl)-3,5-dimethyl-1H-pyrazole (0.135 g, 0.664 mmol). Heat reaction at reflux for 14 hr. under nitrogen. Cool to room temperature and filter over celite. Concentrate filtrate in vacuo and purify residue by flash chromatography eluting with DCM:acetone 6:4 to afford the freebase as a mixture. Purify by reverse phase chromatography (43 g C-18, CH3CN: 1% aqueous TFA 5 to 95% over 20 min.) to afford a mixture. Purify by flash chromatography eluting with chloroform:methanol 0-10% to afford 4-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-ethyl]-3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.150 mg). Dissolve the free base (0.150 g, 0.394 mmol) in acetonitrile (1 mL) and add aqueous 1N HCl (0.433 mL, 0.433 mmol). Stir for 1 h at room temperature. Remove organics and lyophilize to afford the title compound (0.144 g, 77% yield). MS (m/z)=381 [M+H]+.

後処理

  1. temperatureHeat
  2. customreaction
  3. temperatureat reflux for 14 hr
  4. filtrationfilter over celite
  5. customConcentrate filtrate in vacuo and purify residue by flash chromatography
  6. washeluting with DCM:acetone 6:4
  7. customto afford the freebase as a mixture
  8. customPurify by reverse phase chromatography (43 g C-18, CH3CN: 1% aqueous TFA 5 to 95% over 20 min.)
  9. customto afford a mixture
  10. customPurify by flash chromatography
  11. washeluting with chloroform

出典と根拠

ORDレコード
ord-40c3ac2c9dd342c6a727c635d73d2332
出典データセット
uspto-grants-2012_06
特許番号
US08202873B2

反応ノート

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