1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate

HRID 333129Notes

Reaction equation

HRID 333129 reaction equation
Cl.[I:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[CH3:11][C:12]([O:15][C:16]([NH:18][C@H:19]([C:26](O)=[O:27])[CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:17])([CH3:14])[CH3:13].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:12]([O:15][C:16]([NH:18][C@H:19]([C:26]([NH:8][CH2:7][C:6]1[CH:9]=[CH:10][C:3]([I:2])=[CH:4][CH:5]=1)=[O:27])[CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:17])([CH3:13])([CH3:11])[CH3:14]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7018756(S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acidHCID 16217505(4-Iodophenyl)methanamine hydrochloride

Product 1

HCID 68630197(S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoateYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-iodobenzylamine hydrochloride (2.965 g, 11.0 mmol), Boc-Glu(OMe)-OH.DCHA (4.426 g, 10.0 mmol), EDCI (2.301 g, 10.0 mmol), HOBt (1.351 g, 10.0 mmol) in DCM (100 mL) containing DIPEA (5.23 mL) was stirred at room temperature under nitrogen for 20 h. The reaction mixture was diluted with DCM, washed with 1N HCl, sat. NaHCO3 solution, and brine. The solvent was evaporated under reduced pressure to give a crude product, which was purified by flash chromatography eluting with hexane/ethyl acetate (3:1) to give (S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate (3.653 g, 77%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J=8.4 Hz, 2H), 7.00 (d, J=8.4 Hz, 2H), 6.65 (s, 1H), 5.24 (brs, 1H), 4.39 (t, J=5.4 Hz, 2H), 4.15 (m, 1H), 3.70 (s, 3H), 2.57-2.37 (m, 2H), 2.20-2.11 (m, 1H), 1.99-1.90 (m, 1H), 1.44 (s, 9H); MS (ESI), 499 (M+Na)+.

Workup

  1. washwashed with 1N HCl, sat. NaHCO3 solution, and brine
  2. customThe solvent was evaporated under reduced pressure
  3. customto give a crude product, which
  4. customwas purified by flash chromatography
  5. washeluting with hexane/ethyl acetate (3:1)

Sources & evidence

ORD record
ord-9e77cf35d80a4badbc364a6754987d85
Source dataset
uspto-grants-2014_11
Patent number
US08877970B2

Reaction notes

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