Diisopropylethylamine → HCID 46207591, compound

HRID 2209346Notes

Reaction equation

HRID 2209346 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=O)[C@@H:10]([CH3:12])[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.[CH3:115][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>[OH:11][C@H:10]([C@@H:9]([C:13](=[O:15])[NH:133][C@H:129]([C:130]([OH:132])=[O:131])[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])[NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH3:12]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 197465Dab-cyclo(dab-dab-phe-leu-dab-dab-thr) sulfate saltHCID 2724766N-tert-Butoxycarbonyl-L-threonineHCID 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 46207591HCID 46207591, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL round bottom flask, N-Boc-L-threonine (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 and 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 (145 mg, 28%) to yield Compound N-56. 1H-NMR (500 MHz, CD3OD): δ 1.21 (d, J=6 Hz, 3H), 1.48 (s, 9H), 1.62 (bs, 6H), 1.69 (s, 3H), 1.71 (s, 3H), 1.99 (t, J=7.5 Hz, 2H), 2.05-2.22 (m, 6H), 2.82 (dd, J=7.5, 14 Hz), 3.01 (dd, J=5, 13.5 Hz, 1H), 3.17 (dd, J=7, 13.5 Hz, 1H), 3.29 (dd, J=8.5, 13.5 Hz, 1H), 3.33 (bs, 2H), 4.09-4.16 (m, 2H), 4.65 (dd, J=5, 7 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, 19.9, 26.0, 27.4, 27.8, 28.6, 30.4, 33.5, 40.8, 40.9, 53.4, 61.3, 63.0, 68.7, 80.8, 121.6, 125.15, 125.5, 132.12, 136.26, 140.6, 157.9, 173.2, 173.6; ES-MS: mass calcd for Chemical Formula: C27H46N2O6S 526.7. Found (M+Na) m/z 549.4.

Workup

  1. stirringstirred 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-aa4a3608bad24522bfa5288b241c8d8e
Source dataset
uspto-grants-2016_06
Patent number
US09376383B2

Reaction notes

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