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Triethylamine → 1-[2-((3,5-bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one

HRID 409499
ノート
印刷プレビュー

反応式

HRID 409499 の反応式
C(O[C:6]([N:8]1[CH2:12][C@@H:11]([N:13]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:14]2[N:19]=[CH:18][C:17]([N:20]3[CH2:24][CH2:23][N:22]([CH3:25])[C:21]3=[O:26])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:42][CH3:43])=O)(C)(C)C.[ClH:44].CCO[C:48]([CH3:50])=[O:49].FC(F)(F)C1C=[C:55](C=C(C(F)(F)F)C=1)[CH2:56][N:57]([C:65]1[N:70]=[CH:69][C:68](N2CCN(C)C2=O)=C[N:66]=1)[C@@H:58]1CN[C@H](CC)C1.CCN(CC)CC.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(Cl)Cl>[F:36][C:34]([F:35])([F:37])[C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([C:38]([F:40])([F:41])[F:39])[CH:31]=1)[CH2:27][N:13]([C@H:11]1[CH2:10][C@@H:9]([CH2:42][CH3:43])[N:8]([C:6]2[C:68]([Cl:44])=[CH:69][N:70]=[C:65]([N:57]3[CH2:58][CH2:50][CH:48]([OH:49])[CH2:55][CH2:56]3)[N:66]=2)[CH2:12]1)[C:14]1[N:19]=[CH:18][C:17]([N:20]2[CH2:24][CH2:23][N:22]([CH3:25])[C:21]2=[O:26])=[CH:16][N:15]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 59614381(2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 86648406(2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine

生成物 1

HCID 596144061-[2-((3,5-bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one収率 68%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a mixture of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.24 mmol) in EtOAc (1 mL) is added 4N HCl/EtOAc (2.4 mL, 2.44 mmol). After removal of solvent, the mixture is used without further purification. (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine is treated with 2,4,5-trichloro-pyrimide (67.1 mg, 0.37 mmol) and Et3N (0.07 mL, 0.49 mmol) in CH2Cl2 (1 mL) at RT for 12 hours. After adding sat. NaHCO3 (aq.), the mixture is extracted with CH2Cl2, washed with brine and dried (MgSO4). Concentration under vacuum and purification with silica gel column chromatography (eluent: n-hexane:EtOAc=1:1) gives 1-[2-((3,5-Bis-trifluoromethyl-benzyl)-{(3S,5R)-1-[5-chloro-2-(4-hydroxy-piperidin-1-yl)-pyrimidin-4-yl]-5-ethyl-pyrrolidin-3-yl}-amino)-pyrimidin-5-yl]-3-methyl-imidazolidin-2-one (110 mg, 68%)

後処理

  1. customAfter removal of solvent
  2. customthe mixture is used without further purification
  3. extractionthe mixture is extracted with CH2Cl2
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationConcentration
  7. customunder vacuum and purification with silica gel column chromatography (eluent: n-hexane:EtOAc=1:1)

出典と根拠

ORDレコード
ord-dabfe4bd116349aa9e5b6ccecc48e049
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08759365B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート