Formic Acid → Hydroxy{(1S)-4-pyrimidin-2-yl-1-[({4-[5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]piperazin-1-yl}sulfonyl)methyl]butyl}formamide

HRID 1723801ノート

反応式

HRID 1723801 の反応式
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[OH:11][NH:12][CH:13]([CH2:36][CH2:37][CH2:38][C:39]1[N:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH2:14][S:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[CH:28][C:27]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[CH:26][N:25]=2)[CH2:20][CH2:19]1)(=[O:17])=[O:16]>C1COCC1>[OH:11][N:12]([C@H:13]([CH2:14][S:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[CH:28][C:27]([O:30][CH2:31][C:32]([F:33])([F:34])[F:35])=[CH:26][N:25]=2)[CH2:20][CH2:19]1)(=[O:17])=[O:16])[CH2:36][CH2:37][CH2:38][C:39]1[N:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH:1]=[O:2]

参加物

5

反応物 3

HCID 284Formic Acid2 回HCID 7918Acetic AnhydrideHCID 866145742-(4-{[2-(Hydroxyamino)-5-pyrimidin-2-ylpentyl]sulfonyl}piperazin-1-yl)-5-(2,2,2-trifluoroethoxy)pyrimidine

生成物 1

HCID 57559244Hydroxy{(1S)-4-pyrimidin-2-yl-1-[({4-[5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]piperazin-1-yl}sulfonyl)methyl]butyl}formamide収率 71.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To formic acid (114 mL, 3.03 mol) at 0° C. was added acetic anhydride (28.6 mL, 0.303 mol) and the mixture was stirred at RT for 10 minutes. The reaction was then recooled to 0° C., and added to a solution of 2-(4-{[2-(hydroxyamino)-5-pyrimidin-2-ylpentyl]sulfonyl}piperazin-1-yl)-5-(2,2,2-trifluoroethoxy)pyrimidine (30.6 g, 60.5 mmol) and formic acid (114 mL, 3.03 mol) in THF (600 mL). The reaction was brought to room temperature and stirred for one hour. Volatiles were then removed in vacuo, and the residue azeotroped with toluene (2×300 mL). The residue was then dissolved in methanol (300 mL) and heated to 40° C. for one hour. The solution was then cooled to room temperature and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 10% MeOH in EtOAc) to give the racemic compound as a pale orange foam (22.94 g, 43 mmol, 71%).

後処理

  1. customwas then recooled to 0° C.
  2. customwas brought to room temperature
  3. stirringstirred for one hour
  4. customVolatiles were then removed in vacuo
  5. customthe residue azeotroped with toluene (2×300 mL)
  6. dissolutionThe residue was then dissolved in methanol (300 mL)
  7. temperatureheated to 40° C. for one hour
  8. temperatureThe solution was then cooled to room temperature
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by flash chromatography (silica gel, 10% MeOH in EtOAc)

出典と根拠

ORDレコード
ord-6226cf4261ba4b2c85f86287d9f68575
出典データセット
uspto-grants-2009_02
特許番号
US07485644B2

反応ノート

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