Diisopropylethylamine → (R)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxamido)-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)propanoic acid

HRID 2209349

反応式

HRID 2209349 の反応式
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([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.[CH3:115][C:116]([CH3:136])=[CH:117][CH2:118][CH2:119]/[C:120](/[CH3:135])=[CH:121]/[CH2:122][CH2:123]/[C:124](/[CH3:134])=[CH:125]/[CH2:126][S:127][CH2:128][C@H:129]([NH2:133])[C:130]([OH:132])=[O:131]>C(Cl)Cl>[C:4]([O:3][C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([NH:133][C@@H:129]([CH2:128][S:127][CH2:126]/[CH:125]=[C:124](\[CH3:134])/[CH2:123][CH2:122]/[CH:121]=[C:120](\[CH3:135])/[CH2:119][CH2:118][CH:117]=[C:116]([CH3:136])[CH3:115])[C:130]([OH:132])=[O:131])=[O:12])=[O:2])([CH3:5])([CH3:6])[CH3:7]

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 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)

生成物 1

HCID 46209286(R)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxamido)-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)propanoic acid

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a 100 mL round bottom flask, N-Boc-L-proline (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. 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 (232 mg, 44%) to yield Compound N-8. 1H-NMR (500 MHz, CDCl3): δ 1.46 (s, 9H), 1.62 (bs, 6H), 1.69 (s, 3H), 1.72 (s, 3H), 1.89 (bs, 1H), 1.98 (t, J=7.5 Hz, 2H), 2.05-2.14 (m, 6H), 2.24-2.26 (m, 1H), 2.79 (dd, J=8.0, 14.0, 1H), 3.03 (bd, J=13.0 Hz, 1H), 3.15 (dd, J=7.5, 13.0 Hz, 1H), 3.27 (dd, J=8.0, 13.0 Hz, 1H), 3.40 (m, 1H), 3.66 (bs, 1H), 4.28 (bs, 1H), 4.60 (dd, J=4.9, 8.0 Hz, 1H), 5.11-5.14 (m, 2H), 5.24 (t, J=7.4 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.2, 16.3, 17.8, 24.2, 24.5, 25.3, 25.9, 27.4, 27.8, 28.7, 30.1, 30.4, 30.7, 31.1, 32.5, 33.5, 40.8, 40.9, 47.9, 48.3, 53.1, 53.4, 61.4, 61.9, 81.4, 81.7, 121.5, 125.1, 125.5, 132.1, 136.3, 140.5, 156.2, 173.6, 175.8; ES-MS: mass calcd for Chemical Formula: C28H46N2O5S 522.3. Found (M+Na) m/z 545.3.

後処理

  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

出典と根拠

ORDレコード
ord-e3545bac887b40a4b29d01b5e2cd2df8
出典データセット
uspto-grants-2016_06
特許番号
US09376383B2

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