3-Chlorophenol → 5-(3-Chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

HRID 2037008ノート

反応式

HRID 2037008 の反応式
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH:16]2[CH2:18][CH2:17]2)C(=O)OC(C)(C)C)[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1.[Cl:24][C:25]1[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>O.CN1C(=O)CCC1>[Cl:24][C:25]1[CH:26]=[C:27]([CH:28]=[CH:29][CH:30]=1)[O:31][C:2]1[CH:7]=[C:6]([NH:8][CH:16]2[CH2:17][CH2:18]2)[N:5]2[N:19]=[CH:20][C:21]([CH:22]=[O:23])=[C:4]2[N:3]=1

参加物

7

反応物 4

HCID 79333-ChlorophenolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 58196421Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

生成物 1

HCID 583139015-(3-Chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde収率 65%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (1.0 eq, 49 mg, 0.145 mmol) was mixed in a vial with NMP (0.2 ml), 3-chlorophenol (5.0 eq, 93 mg, 0.274 mmol) and potassium carbonate (5.0 eq, 100 mg, 0.723 mmol). The reaction mixture was stirred at room temperature for one hour. Water was added and the resulting gummy material was extracted with methylene chloride. The organic phase was dried over Na2SO4 and the volatiles removed in vacuo. The resulting NMP solution was reacted with a HCl 4N solution in dioxane (5 ml) at room temperature for one hour, at which time LCMS monitoring indicated completion of the reaction. The reaction was treated with water and 6N NaOH and stirred overnight at room temperature. The solid was filtered and dried to afford crude 5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde as a solid (31 mg). The material was heated with hydantoin (30 mg), piperidine (30 uL) in Ethanol (1 ml) in a vial at 90° C. for seven hours. Water was added and the material was filtered, washed with ethanol, ethanol/water and dried. (Z)-5-((5-(3-chlorophenoxy)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)imidazolidine-2,4-dione was isolated as solid (43 mg, 38% over 2 steps).). LCMS (ES):>95% pure, m/z 411 [M+H]+.

後処理

  1. extractionthe resulting gummy material was extracted with methylene chloride
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customthe volatiles removed in vacuo
  4. customThe resulting NMP solution was reacted with a HCl 4N solution in dioxane (5 ml) at room temperature for one hour, at which time LCMS
  5. customcompletion of the reaction
  6. stirringstirred overnight at room temperature
  7. filtrationThe solid was filtered
  8. customdried

出典と根拠

ORDレコード
ord-628ab0ff9db346249d03ca65ad2954df
出典データセット
uspto-grants-2013_11
特許番号
US08575177B2

反応ノート

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