N-(tert-butoxycarbonyl)glycine → (R,13E,17E)-2,2,14,18,22-pentamethyl-4,7-dioxo-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

HRID 388161Notes

Reaction equation

HRID 388161 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].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.[CH3:112][C:113]([CH3:133])=[CH:114][CH2:115][CH2:116]/[C:117](/[CH3:132])=[CH:118]/[CH2:119][CH2:120]/[C:121](/[CH3:131])=[CH:122]/[CH2:123][S:124][CH2:125][C@H:126]([NH2:130])[C:127]([OH:129])=[O:128]>C(Cl)Cl>[CH3:4][C:2]([CH3:1])([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10](=[O:12])[NH:130][C@H:126]([C:127]([OH:129])=[O:128])[CH2:125][S:124][CH2:123]/[CH:122]=[C:121](\[CH3:131])/[CH2:120][CH2:119]/[CH:118]=[C:117](\[CH3:132])/[CH2:116][CH2:115][CH:114]=[C:113]([CH3:133])[CH3:112])[CH3:3]

Participants

7

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 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 59410825(R,13E,17E)-2,2,14,18,22-pentamethyl-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-glycine (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 and 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 (78 mg, 18%) to yield Compound N-4. 1H-NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 1.60 (bs, 6H), 1.67 (s, 3H), 1.68 (s, 3H), 1.97 (t, J=7.5 Hz, 2H), 2.01-2.15 (m, 6H), 2.85 (bd, J=13 Hz, 1H), 3.01 (bd, J=13 Hz, 1H), 3.14-3.23 (m, 2H), 3.81 (d, J=16.5 Hz), 4.01 (d, J=12 Hz, 1H), 4.77 (m, 1H), 5.09 (m, 2H), 5.30 (1H). 13C-NMR (125 MHz, CDCl3): δ 16.0, 16.1, 17.7, 25.7, 26.5, 26.7, 28.4, 30.0, 32.9, 39.7, 39.7, 43.8, 51.7, 80.7, 119.5, 123.8, 124.3, 131.4, 135.4, 140.1, 156.3, 169.8, 172.9; ES-MS: mass calcd for Chemical Formula: C25H42N2O5S 482.3. Found (M+Na) m/z 505.1.

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-f896079da71340b6bf964b95c4215547
Source dataset
uspto-grants-2013_02
Patent number
US08372884B2

Reaction notes

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