Trifluoroacetic acid → 4-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide

HRID 901474

반응식

HRID 901474 반응식
C(OC([N:8]1[CH2:12][CH:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:9]1)=O)(C)(C)C.[NH2:18][CH:19]([CH:23]1[CH:28]([OH:29])[CH:27]([OH:30])[CH:26]([OH:31])[CH:25]([CH2:32][CH2:33][CH3:34])[O:24]1)[CH:20]([CH3:22])[CH3:21].C(N(CC)CC)C.FC(F)(F)[C:44](=N[Si](C)(C)C)[O:45][Si](C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O>CN(C=O)C.O.ClCCCl>[CH3:21][CH:20]([CH3:22])[CH:19]([NH:18][C:44]([CH:9]1[CH2:10][CH:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:12][NH:8]1)=[O:45])[CH:23]1[CH:28]([OH:29])[CH:27]([OH:30])[CH:26]([OH:31])[CH:25]([CH2:32][CH2:33][CH3:34])[O:24]1

참가 물질

10

반응물 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 184464112-(1-Amino-2-methyl-propyl)-6-propyl-tetrahydro-pyran-3,4,5-triolHCID 668180264-Pentyl-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 112237364-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide수율 43%

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

2-Methyl-1-(3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-propylcarbamoyl]-4-pentyl-pyrrolidine-1-carboxylic acid tert-butyl ester. To a solution of 2-(1-Amino-2-methyl-propyl)-6-propyl-tetrahydro-pyran-3,4,5-triol prepared by general method AB (51.9 mg, 0.21 mmol, 1 equiv) in dry DMF (4.5 mL) at 0° C. was added triethylamine (117 μL, 0.84 mmol, 4 equiv), followed by the addition of BSTFA (84 μL, 0.32 mmol, 1.5 equiv). The reaction mixture was stirred at 0° C. for 10 minutes, and then was stirred at rt for 45 minutes. To the reaction mixture was added the protected amino acid 7d as prepared in general method L (R9=n-pentyl, P=Boc) (72 mg, 0.25 mmol, 1.2 equiv) and HATU (120 mg, 0.32 mmol, 1.5 equiv). The reaction mixture was stirred at rt for 2 h, evaporated to dryness, taken up in Et2O (150 mL), washed with 10% citric acid (1×), saturated NaHCO3 (1×) and brine. The organic layer was dried over MgSO4 and concentrated to give the crude product (190 mg) as a yellow oil. The residue was taken up DCE (6 mL), trifluoroacetic acid (4 mL) containing water (0.2 mL) was added with stirring. The reaction mixture was stirred at rt for 1 h, then solvent was removed under vacuum by repeated co-evaporation from DCE. The residue was purified by column chromatography on silica 10% 0.25M NH3 in MeOH/DCM to give the product (38.4 mg, 43%).

후처리

  1. stirringwas stirred at rt for 45 minutes
  2. stirringThe reaction mixture was stirred at rt for 2 h
  3. customevaporated to dryness
  4. washwashed with 10% citric acid (1×), saturated NaHCO3 (1×) and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customto give the crude product (190 mg) as a yellow oil
  8. additionwas added
  9. stirringwith stirring
  10. stirringThe reaction mixture was stirred at rt for 1 h
  11. customsolvent was removed under vacuum
  12. customThe residue was purified by column chromatography on silica 10% 0.25M NH3 in MeOH/DCM

출처 및 근거

ORD 기록
ord-4b7af5cc420d4c729bdc03750d28d7d0
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07361743B2

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