Diisopropylethylamine → (6S,9R,13E,17E)-2,2,14,18,22-pentamethyl-4,7-dioxo-6-phenyl-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

In a 100 mL round bottom flask, N-Boc-L-phenylglycine (1.0 mmol), coupling reagent (520 mg of PBOP or 380 mg of HATU, 1 mmol) and N,N-diisopropyl-ethyl-amine (650 mg, 5 mmol) were mixed in CH2Cl2 (10 mL). The reaction mixture was stirred at room temperature for 30 minutes and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) was added. The reaction mixture was stirred at room temperature overnight. CH2Cl2 was removed by rotary evaporation. The resulting residue was dissolved in ethyl acetate (50 mL). The organic solution was washed with an NH4Cl saturated solution (50 mL), dried over Na2SO4, and concentrated to afford a crude mixture. The crude mixture was purified by preparative HPLC (118 mg, 21%) to yield Compound N-5. 1H-NMR (500 MHz, CD3OD): δ 1.47 (s, 9H), 1.62 (s, 6H), 1.69 (s, 6H), 1.99 (t, J=7.0 Hz, 2H), 2.03-2.13 (m, 6H), 2.81 (dd, J=8.1, 13.9 Hz, 1H), 3.01 (dd, J=6.8, 12.1 Hz, 1H), 3.16 (dd, J=7.6, 13.2 Hz, 1H), 3.26 (dd, J=8.5, 13.4 Hz), 4.62 (bt, J=5.5), 5.09-5.12 (m, 2H), 5.22 (t, J=7.9 Hz, 1H), 7.29-7.37 (m, 3H), 7.46 (d, J=7.3 Hz, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.2, 16.3, 25.9, 27.3, 27.8, 28.7, 30.3, 33.4, 33.5, 40.8, 40.9, 53.6, 59.9, 81.1, 121.6, 125.2, 125.5, 128.6, 129.1, 129.7, 132.1, 136.3, 139.1, 140.5, 158.3, 173.0, 173.4; ES-MS: mass calcd for Chemical Formula: C31H46N2O5S 558.8. Found (M+Na) m/z 581.4.

1. stirringThe reaction mixture was stirred at room temperature overnight
2. customCH2Cl2 was removed by rotary evaporation
3. dissolutionThe resulting residue was dissolved in ethyl acetate (50 mL)
4. washThe organic solution was washed with an NH4Cl saturated solution (50 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated

ORDレコード

ord-0f28447bd23041d587071d237d711be5

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09376383B2