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

HRID 388157

Reaction equation

HRID 388157 reaction equation
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][S:12][CH3:13])([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>[CH3:7][C:4]([CH3:5])([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:10][CH2:11][S:12][CH3:13])[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])[CH3:6]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 89857Boc-L-methionineHCID 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)

Product 1

HCID 59410815(6S,9R,13E,17E)-2,2,14,18,22-pentamethyl-6-(2-(methylthio)ethyl)-4,7-dioxo-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL round bottom flask, N-Boc-L-methionine (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 (290 mg, 52%) to yield Compound N-57. 1H-NMR (500 MHz, CDCl3): δ 1.47 (s, 9H), 1.62 (bs, 6H), 1.69 (s, 3H), 1.72 (s, 3H), 1.90-1.93 (m, 1H), 1.99 (t, J=7.5 Hz, 2H), 2.03-2.16 (m, 8H), 2.50-2.68 (m, 2H), 2.80 (dd, J=8, 14 Hz, 1H), 3.02 (dd, J=4.5, 14 Hz, 1H), 3.18 (dd, J=7, 13 Hz, 1H), 3.27 (dd, J=8, 13 Hz, 1H), 3.25 (dd, J=5, 8 Hz, 1H), 4.60 (dd, J=4.5, 8, 1H), 5.10-5.15 (m, 2H), 5.24 (t, J=7.5, 1H). 13C-NMR (125 MHz, CDCl3): δ 15.3, 16.2, 16.3, 17.8, 26.0, 27.4, 27.8, 28.8, 30.3, 31.0, 33.0, 33.4, 40.8, 40.9, 53.3, 55.1, 80.8, 121.6, 125.2, 125.5, 132.1, 136.3, 140.6, 157.8, 173.6, 174.6; ES-MS: mass calcd for Chemical Formula: C28H48N2O5S2 556.3. Found (M+Na) m/z 279.2.

Workup

  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

Sources & evidence

ORD record
ord-72344870183145d1ac5328cf6aa95b9a
Source dataset
uspto-grants-2013_02
Patent number
US08372884B2

Linked notes

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