5-Aminopentan-1-ol → HCID 68292892, compound

HRID 529465Notes

Reaction equation

HRID 529465 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([C:23]([CH3:45])([S:25][C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH3:24])[C:20]([OH:22])=O)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][OH:71]>CCOC(C)=O.C(Cl)Cl.CN(C=O)C>[OH:71][CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][NH:65][C:20](=[O:22])[C@@H:19]([NH:18][C:16](=[O:17])[O:15][CH2:14][CH:12]1[C:13]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[C:6]2[C:11]1=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:23]([CH3:24])([S:25][C:26]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH3:45]

Participants

8

Reactant 4

HCID 756345-Aminopentan-1-olHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 44593786N-{[(9H-Fluoren-9-yl)methoxy]carbonyl}-3-[(triphenylmethyl)sulfanyl]-L-valine

Product 1

HCID 68292892HCID 68292892, compoundYield 65.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask was added (R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-methyl-3-(tritylthio)butanoic acid (400 mg, 0.652 mmol), HOBT (120 mg, 0.782 mmol), Hunig's Base (0.137 mL, 0.782 mmol), DMF (1 mL) and DCM (5 mL). The reaction was stirred at rt for 1 hr. Then 5-aminopentan-1-ol (67.2 mg, 0.652 mmol) was added to the reaction and the reaction was stirred at rt overnight. The reaction was diluted with EtOAc (50 mL) and washed with water (4×15 mL) and saturated aqueous NaCl (15 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (R)-(9H-fluoren-9-yl)methyl 1-(5-hydroxypentylamino)-3-methyl-1-oxo-3-(tritylthio)butan-2-ylcarbamate (300 mg, 0.429 mmol, 65.9% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.76 (d, J=7.70 Hz, 2H), 7.69-7.50 (m, 8H), 7.39 (t, J=7.42 Hz, 2H), 7.33-7.15 (m, 11H), 5.74-5.41 (m, 2H), 4.45-4.11 (m, 3H), 3.67-3.39 (m, 2H), 3.35-3.07 (m, 2H), 1.56-1.41 (m, 4H), 1.42-1.31 (m, 2H), 1.33-1.24 (m, 2H), 1.18 (br. s., 3H), 1.11 (s, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 144.86, 141.28, 129.96, 127.86, 127.69, 127.07, 126.76, 125.11, 119.95, 68.35, 62.48, 53.38, 47.11, 39.35, 32.11, 29.01, 26.43, 22.93, 22.69, 14.09.

Workup

  1. stirringthe reaction was stirred at rt overnight
  2. washwashed with water (4×15 mL) and saturated aqueous NaCl (15 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified
  8. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-b6dbc4901c6d4c6e80218b440eea2792
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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