2,4-Dichlorobenzylamine → Gsk1370319A

HRID 554076노트

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HRID 554076 반응식
[CH3:1][N:2]1[C:9](=[O:10])[CH2:8][CH2:7][C@H:3]1[C:4]([OH:6])=O.ON1C2C=CC=CC=2N=N1.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[CH2:29][NH2:30].C(NC(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl.CS(C)=O.C(#N)C>[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[CH2:29][NH:30][C:4](=[O:6])[C@@H:3]1[CH2:7][CH2:8][C:9](=[O:10])[N:2]1[CH3:1]

참가 물질

9

반응물 5

HCID 14852,4-DichlorobenzylamineHCID 7912DiisopropylamineHCID 757711-HydroxybenzotriazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18649403(2S)-1-methyl-5-oxopyrrolidine-2-carboxylic acid

생성물 1

HCID 67461788Gsk1370319A수율 70.6%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

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온도
20 °C

실험 절차

1-Methyl-5-oxo-proline (0.057 g, 0.4 mmol, prepared as described below) was dissolved in anhydrous dichloromethane (6 ml) and to this was added 1-hydroxybenzotriazole (0.060 g, 0.4 mmol), [(2,4-dichloro-phenyl)methyl]amine (0.055 ml, 0.4 mmol), diisopropylamine (0.140 ml, 0.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.152 g, 0.4 mmol). The mixture was stirred at room temperature (20° C.) under argon for 3 hrs and then overnight. The mixture was diluted with more dichloromethane (25 ml) and washed sequentially with 2M aqueous hydrogen chloride (20 ml), saturated aqueous sodium hydrogen carbonate (20 ml), 10% aqueous sodium carbonate (20 ml) and brine (20 ml). The organic layer was filtered through a hydrophobic frit and then evaporated to give the crude product. The crude material was dissolved in a mixture of dimethylsulphoxide (0.9 ml) and acetonitrile (0.9 ml) and then purified by mass-directed automated HPLC to give pure N-[(2,4-dichlorophenyl)methyl]-1-methyl-5-oxo-prolinamide (0.085 g) as a white solid. LC/MS [M+H]+=301, retention time=2.16 minutes.

후처리

  1. customovernight
  2. washwashed sequentially with 2M aqueous hydrogen chloride (20 ml), saturated aqueous sodium hydrogen carbonate (20 ml), 10% aqueous sodium carbonate (20 ml) and brine (20 ml)
  3. filtrationThe organic layer was filtered through a hydrophobic frit
  4. customevaporated
  5. customto give the crude product
  6. custompurified

출처 및 근거

ORD 기록
ord-265cbaacd23e4bdc9fd0dcecbe7c6695
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08048907B2

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