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Triethylamine → (3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158361
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HRID 1158361 반응식
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N+:25]([C:28]1[CH:29]=[C:30]([CH2:34][C:35]([OH:37])=O)[CH:31]=[CH:32][CH:33]=1)([O-:27])=[O:26].[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:70])[CH3:69])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][NH:72][CH:73]2[CH2:75][CH2:74]2)[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CC#N>[C:38]([O:42][C:43]([N:45]1[CH2:49][C@@H:48]([CH2:50][N:51]([CH:68]([CH3:69])[CH3:70])[C:52](=[O:67])[C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=2)[C@H:47]([CH2:71][N:72]([CH:73]2[CH2:74][CH2:75]2)[C:35](=[O:37])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([N+:25]([O-:27])=[O:26])[CH:29]=2)[CH2:46]1)=[O:44])([CH3:40])([CH3:41])[CH3:39]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 158763-Nitrophenylacetic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68616408(3R*,4R*)-3-Cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 68618278(3R*,4R*)-3-({Cyclopropyl-[2-(3-nitro-phenyl)-acetyl]-amino}-methyl)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

At 0° C. HBTU (426 mg, 1.12 mmol) is added to a solution of 3-nitrophenylacetic acid (187 mg, 1.03 mmol) in CH3CN (10 mL) and the resulting solution is stirred for 10 min. Then a solution of (3R*,4R*)-3-cyclopropylaminomethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.2 g, 0.375 mmol). (500 mg, 0.94 mmol) and triethylamine (1.04 mL, 7.5 mmol) in CH3CN (10 mL) is added at 0° C. and the reaction mixture is stirred at RT for another 2 h. For workup a sat. solution of NaHCO3 is added and the mixture is extracted with ethyl acetate. Washing of the combined extracts with brine, drying (Na2SO4), filtration and evaporation of the solvent affords the crude product which is purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1) to give the title compound. MS (LC-MS): 597.0 [M+H-Boc]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mumin): 6.47 min.

후처리

  1. customAt 0° C
  2. stirringthe reaction mixture is stirred at RT for another 2 h
  3. extractionthe mixture is extracted with ethyl acetate
  4. washWashing of the combined extracts with brine
  5. customdrying
  6. filtration(Na2SO4), filtration and evaporation of the solvent
  7. customaffords the crude product which
  8. customis purified by flash chromatography on silica gel (eluent: CH2Cl2 to CH2Cl2/MeOH 9:1)

출처 및 근거

ORD 기록
ord-a925cdd059e0493ca4e04e3ee1862e1c
출처 데이터셋
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07807709B2

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