(S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate → (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate

HRID 333130Notes

Reaction equation

HRID 333130 reaction equation
C(OC([NH:8][C@H:9]([C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][CH:21]=1)=[O:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH2:8][C@H:9]([C:16]([NH:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([I:26])=[CH:24][CH:25]=1)=[O:17])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

4

Reactant 1

HCID 68630197(S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate

Product 1

HCID 68858394(S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoateYield 99.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate (2.129 g, 4.47 mmol) in DCM (15 mL) and TFA (10 mL) was stirred at room temperature for 4 h. After the solvent was evaporated, the reaction mixture was diluted with DCM, washed with sat. K2CO3 aqueous solution and concentrated in vacuo to afford (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g). A solution of (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g), Boc-Glu(OMe)—OH.DCHA (1.97 g, 4.44 mmol), EDCI (1.02 g, 5.33 mmol), HOBt (0.599 g, 4.44 mmol) in DCM (100 mL) containing DIPEA (2.26 mL) was stirred at room temperature under nitrogen for 20 h. The reaction mixture was diluted with DCM, washed with 1N HCl aqueous solution, sat. NaHCO3 aqueous solution and brine. The organic phase was separated and evaporated under reduced pressure to give a crude product, which was purified by flash chromatography with hexane/ethyl acetate as eluent to give (S)-methyl 4-(tert-butoxycarbonylamino)-5-((S)-1-(4-iodobenzylamino)-5-methoxy-1,5-dioxopentan-2-ylamino)-5-oxopentanoate (2.137 g, 77% over 2 steps) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=8.4 Hz, 2H), 7.20 (s, 1H), 7.00 (d, J=8.4 Hz, 2H), 5.44 (brs, 1H), 4.48-4.30 (m, 3H), 4.06-4.02 (m, 1H), 3.69 (s, 6H), 2.54-2.37 (m, 4H), 2.20-1.93 (m, 3H), 1.37 (s, 9H); MS (ESI), 620 (M+H)+.

Workup

  1. customAfter the solvent was evaporated
  2. additionthe reaction mixture was diluted with DCM
  3. washwashed with sat. K2CO3 aqueous solution
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c6f52c35bfe4432482199769135e9c8d
Source dataset
uspto-grants-2014_11
Patent number
US08877970B2

Reaction notes

Loading…