反応式
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[C@@H](O)[C@@H]1NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2C=CC=CC=2)NC(=O)[C@H](CCN)NC(=O)[C@@H](NC([C@@H](N)CCN)=O)CCNC1=O.OS(O)(=O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:116][C:117]([CH3:137])=[CH:118][CH2:119][CH2:120]/[C:121](/[CH3:136])=[CH:122]/[CH2:123][CH2:124]/[C:125](/[CH3:135])=[CH:126]/[CH2:127][S:128][CH2:129][C@H:130]([NH2:134])[C:131]([OH:133])=[O:132]>C(Cl)Cl>[CH2:10]([C@@H:9]([C:14](=[O:16])[NH:134][C@H:130]([C:131]([OH:133])=[O:132])[CH2:129][S:128][CH2:127]/[CH:126]=[C:125](\[CH3:135])/[CH2:124][CH2:123]/[CH:122]=[C:121](\[CH3:136])/[CH2:120][CH2:119][CH:118]=[C:117]([CH3:137])[CH3:116])[NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH:11]([CH3:12])[CH3:13]参加物
反応物 5
HCID 81531Diisopropylethylamine
HCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-
HCID 197465Dab-cyclo(dab-dab-phe-leu-dab-dab-thr) sulfate salt
HCID 6438372Farnesylcysteine
HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)生成物 1
試薬・触媒・溶媒 1
実験手順
In a 100 mL round bottom flask, N-Boc-L-leucine (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. S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) was added to the reaction mixture. The reaction mixture was stirred at room temperature overnight, the 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 (200 mg, 37%) to yield Compound N-58. 1H-NMR (500 MHz, CDCl3): δ 0.95 (d, J=6.5 Hz, 3H), 0.98 (d, J=6.5 Hz, 3H), 1.47 (s, 9H), 1.62 (bs, 6H), 1.51-1.59 (m, 1H), 1.69 (s, 3H), 1.72 (s, 3H), 1.99 (t, J=7.5 Hz, 2H), 2.05-2.14 (m, 8H), 2.79 (dd, J=7.5, 14.2, 1H), 3.00 (dd, J=4.8, 13.9 Hz, 1H), 3.17 (dd, J=7.6, 13.0 Hz, 1H), 3.25 (dd, J=8.2, 12.9 Hz, 1H), 4.15 (dd, J=5.4, 9.8 Hz, 1H), 4.60 (dd, J=4.9, 8.0 Hz, 1H), 5.09-5.25 (m, 2H), 5.23 (t, J=7.6 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.2, 16.3, 17.8, 22.0, 23.5, 25.9, 27.4, 27.8, 28.8, 30.4, 33.6, 40.8, 40.9, 42.3, 53.3, 54.6, 80.6, 121.6, 125.2, 125.5, 132.1, 136.2, 140.6, 157.8, 173.6, 175.6; ES-MS: mass calcd for Chemical Formula: C29H50N2O5S 538.3. Found (M+Na) m/z 561.4.
後処理
- stirringThe reaction mixture was stirred at room temperature overnight
- customthe CH2Cl2 was removed by rotary evaporation
- dissolutionThe resulting residue was dissolved in ethyl acetate (50 mL)
- washThe organic solution was washed with an NH4Cl saturated solution (50 mL)
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customto afford a crude mixture
- customThe crude mixture was purified by preparative HPLC (200 mg, 37%)
出典と根拠
- ORDレコード
- ord-9678543578784ea59bd9287d603d1ea9
- 出典データセット
- uspto-grants-2013_02
- 特許番号
- US08372884B2
関連ノート
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