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

HRID 388156

반응식

HRID 388156 반응식
[C:1]([NH:8][C@H:9]([C:12]([OH:14])=O)[CH2:10][OH:11])([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.[CH3:114][C:115]([CH3:135])=[CH:116][CH2:117][CH2:118]/[C:119](/[CH3:134])=[CH:120]/[CH2:121][CH2:122]/[C:123](/[CH3:133])=[CH:124]/[CH2:125][S:126][CH2:127][C@H:128]([NH2:132])[C:129]([OH:131])=[O:130]>C(Cl)Cl>[OH:11][CH2:10][C@@H:9]([C:12](=[O:14])[NH:132][C@H:128]([C:129]([OH:131])=[O:130])[CH2:127][S:126][CH2:125]/[CH:124]=[C:123](\[CH3:133])/[CH2:122][CH2:121]/[CH:120]=[C:119](\[CH3:134])/[CH2:118][CH2:117][CH:116]=[C:115]([CH3:135])[CH3:114])[NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 197465Dab-cyclo(dab-dab-phe-leu-dab-dab-thr) sulfate saltHCID 6438372FarnesylcysteineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

생성물 1

HCID 46208614(6S,9R,13E,17E)-6-(hydroxymethyl)-2,2,14,18,22-pentamethyl-4,7-dioxo-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In a 100 mL round bottom flask, N-Boc-L-serine (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 and the CH2Cl2 was removed by rotary evaporation. The remaining residue was dissolved in ethyl acetate (50 mL). The resulting 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 (51 mg, 10%) to yield Compound N-55. 1H-NMR (500 MHz, CD3OD): δ 1.47 (s, 9H), 1.62 (bs, 6H), 1.69 (s, 3H), 1.71 (s, 3H), 1.99 (t, J=7 Hz, 2H), 2.05-2.22 (m, 6H), 2.81 (dd, J=7.5, 14 Hz, 1H), 3.01 (dd, J=4, 14.5 Hz, 1H), 3.17 (dd, J=7, 13 Hz, 1H), 3.27 (dd, J=8, 12.5 Hz, 1H), 3.33 (bs, 2H), 3.74-3.80 (m, 2H), 4.22 (t, J=5 Hz, 1H), 4.63 (dd, J=5, 7.5 Hz, 1H), 5.11 (m, 2H), 5.23 (t, J=7.5 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.2, 16.3, 17.8, 26.0, 27.4, 27.8, 28.7, 30.4, 33.6, 40.8, 40.9, 53.3, 58.0, 59.6, 63.4, 80.9, 121.6, 125.2, 125.5, 132.1, 136.3, 140.6, 157.8, 173.0, 173.8; ES-MS: mass calcd for Chemical Formula: C26H44N2O6S 512.7. Found (M+Na) m/z 535.4.

후처리

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customthe CH2Cl2 was removed by rotary evaporation
  3. dissolutionThe remaining residue was dissolved in ethyl acetate (50 mL)
  4. washThe resulting organic solution was washed with an NH4Cl saturated solution (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a crude mixture
  8. customThe crude mixture was purified by preparative HPLC (51 mg, 10%)

출처 및 근거

ORD 기록
ord-b8d4c102ae7c4c5fa36a7a467c9d1a74
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372884B2

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