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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
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HRID 409499 반응식
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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 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

생성물 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-one수율 68%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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%)

후처리

  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)

출처 및 근거

ORD 기록
ord-dabfe4bd116349aa9e5b6ccecc48e049
출처 데이터셋
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08759365B2

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