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

HRID 333130노트

반응식

HRID 333130 반응식
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]

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-c6f52c35bfe4432482199769135e9c8d
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877970B2

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