Diisopropylethylamine → HCID 46208243, compound

HRID 2209362Notes

Reaction equation

HRID 2209362 reaction equation
Cl[S:2]([C:5]1[CH:14]=[CH:13][CH:12]=[CH:11][C:6]=1[C:7]([O:9]C)=[O:8])(=[O:4])=[O:3].[CH3:15][C:16]([CH3:36])=[CH:17][CH2:18][CH2:19]/[C:20](/[CH3:35])=[CH:21]/[CH2:22][CH2:23]/[C:24](/[CH3:34])=[CH:25]/[CH2:26][S:27][CH2:28][C@H:29]([NH2:33])[C:30]([OH:32])=[O:31].C(N(CC)C(C)C)(C)C.O[Li].O>C1COCC1.C(OCC)(=O)C.O>[C:30]([C@@H:29]([NH:33][S:2]([C:5]1[CH:14]=[CH:13][CH:12]=[CH:11][C:6]=1[C:7]([OH:9])=[O:8])(=[O:4])=[O:3])[CH2:28][S:27][CH2:26]/[CH:25]=[C:24](\[CH3:34])/[CH2:23][CH2:22]/[CH:21]=[C:20](\[CH3:35])/[CH2:19][CH2:18][CH:17]=[C:16]([CH3:15])[CH3:36])([OH:32])=[O:31]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 117830Benzoic acid, 2-(chlorosulfonyl)-, methyl esterHCID 168937Lithium hydroxide, monohydrateHCID 6438372Farnesylcysteine

Product 1

HCID 46208243HCID 46208243, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a 100 mL round bottom flask, to a solution of methyl 2-(chlorosulfonyl)benzoate (281 mg, 1.2 mmol) and S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) in THF (5 mL) was added N,N-diisopropyl-ethyl-amine (0.52 mL, 3 mmol) dropwise. The solution was stirred at room temperature for 4 h. The mixture was diluted with ethyl acetate (60 mL) and washed sequentially with an NH4Cl saturated solution (10 mL×2), H2O (10 mL×1) and brine (10 mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The resulting residue was dissolved in THF (3 mL) and a solution of LiOH.H2O (210 mg, 5 mmol) in H2O (2 mL) was added slowly at 0° C. The reaction was left at room temperature overnight. The reaction was quenched with 1 N HCl and pH was adjusted to 2.0. The solution was then extracted by ethyl acetate (30 mL×3). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was then further purified by preparative HPLC (290 mg, 57%) to yield Compound N-81. 1H-NMR (500 MHz, CD3OD): δ 1.50 (s, 6H), 1.55 (s, 3H), 1.57 (s, 3H), 1.86-1.89 (m, 2H), 1.94-2.02 (m, 6H), 2.71 (dd, J=6.0, 14.0 Hz, 1H), 2.77 (dd, J=5.5, 14.0 Hz, 1H), 3.01-3.08 (m, 2H), 4.10 (t, J=6.0 Hz, 1H), 5.00-5.06 (m, 3H), 7.56-7.62 (m, 2H), 7.84 (d, J=6.5 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H). 13C-NMR (125 MHz, CD3OD): δ 16.17, 16.28, 17.81, 24.24, 25.96, 27.36, 27.78, 30.52, 34.79, 40.75, 40.89, 57.80, 121.53, 125.14, 125.46, 130.07, 132.13, 132.56, 133.78, 136.28, 140.63, 140.72, 170.16, 173.07; ES-MS: mass calcd for Chemical Formula: C25H35NO6S2 509.68. Found (M+Na) m/z 532.1.

Workup

  1. washwashed sequentially with an NH4Cl saturated solution (10 mL×2), H2O (10 mL×1) and brine (10 mL×1)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in THF (3 mL)
  5. waitThe reaction was left at room temperature overnight
  6. customThe reaction was quenched with 1 N HCl and pH
  7. extractionThe solution was then extracted by ethyl acetate (30 mL×3)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was then further purified by preparative HPLC (290 mg, 57%)
  11. customto yield Compound N-81

Sources & evidence

ORD record
ord-da4d741f47e646e79cb6832213914255
Source dataset
uspto-grants-2016_06
Patent number
US09376383B2

Reaction notes

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