Diisopropylethylamine → HCID 46208096, compound

HRID 388167Notes

Reaction equation

HRID 388167 reaction equation
CC[O:3][C:4]([CH2:6][CH2:7][N:8]=[C:9]=[S:10])=[O:5].[CH3:11][C:12]([CH3:32])=[CH:13][CH2:14][CH2:15]/[C:16](/[CH3:31])=[CH:17]/[CH2:18][CH2:19]/[C:20](/[CH3:30])=[CH:21]/[CH2:22][S:23][CH2:24][C@H:25]([NH2:29])[C:26]([OH:28])=[O:27].C(N(CC)C(C)C)(C)C.O[Li].O>C1COCC1.C(OCC)(=O)C.O>[C:4]([CH2:6][CH2:7][NH:8][C:9](=[S:10])[NH:29][C@@H:25]([CH2:24][S:23][CH2:22]/[CH:21]=[C:20](\[CH3:30])/[CH2:19][CH2:18]/[CH:17]=[C:16](\[CH3:31])/[CH2:15][CH2:14][CH:13]=[C:12]([CH3:32])[CH3:11])[C:26]([OH:28])=[O:27])([OH:3])=[O:5]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 526514Ethyl 3-isothiocyanatopropionateHCID 6438372Farnesylcysteine

Product 1

HCID 46208096HCID 46208096, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

In a 100 mL round bottom flask, to a suspension of ethyl-3-isothiocynato propionate (1 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.87 mL, 5 mmol) dropwise. The solution was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo to afford crude Compound N-74. The crude Compound N-74 obtained above was dissolved in THF (3 mL) and a solution of LiOH.H2O (126 mg, 3 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left for 4 h. The solution was then diluted with ethyl acetate (60 mL) and washed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was then further purified by preparative HPLC (230 mg, 50%) to yield Compound N-74. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 3H), 1.51 (s, 3H), 1.57 (s, 3H), 1.59 (s, 3H), 1.86-2.04 (m, 8H), 2.53 (t, J=6.0 Hz, 2H), 2.77 (dd, J=6.5, 14.0 Hz, 1H), 2.94-2.95 (m, 1H), 3.05-3.06 (m, 1H), 3.15-3.17 (m, 1H), 3.67 (broad, 2H), 5.00-5.01 (m, 2H), 5.09-5.14 (m, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.30, 17.81, 25.96, 27.39, 27.79, 30.68, 31.57, 32.81, 33.20, 33.90, 34.56, 37.55, 40.80, 40.89, 57.93, 61.05, 121.34, 121.70, 125.48, 132.11, 136.24, 140.52, 173.76, 174.55, 175.68; ES-MS: mass calcd for Chemical Formula: C22H36N2O4S2 456.66. Found (M+) m/z 457.2, (M+Na) m/z 479.2.

Workup

  1. washwashed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto afford crude Compound N-74
  5. customobtained
  6. waitThe reaction was left for 4 h
  7. washwashed by 0.5 N HCl (10 mL×1), H2O (10 mL×1) and brine (10 mL×1)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was then further purified by preparative HPLC (230 mg, 50%)
  11. customto yield Compound N-74

Sources & evidence

ORD record
ord-6bc281d4ea9f40b1bb3462fce208a441
Source dataset
uspto-grants-2013_02
Patent number
US08372884B2

Reaction notes

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