5-Hydroxyindoleacetic Acid → (R)-2-(2-(5-hydroxy-1H-indol-3-yl)acetamido)-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)propanoic acid

HRID 1482467

Reaction equation

HRID 1482467 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([OH:14])=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.[CH3:48][C:49]([CH3:69])=[CH:50][CH2:51][CH2:52]/[C:53](/[CH3:68])=[CH:54]/[CH2:55][CH2:56]/[C:57](/[CH3:67])=[CH:58]/[CH2:59][S:60][CH2:61][C@H:62]([NH2:66])[C:63]([OH:65])=[O:64]>C1COCC1>[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([NH:66][C@@H:62]([CH2:61][S:60][CH2:59]/[CH:58]=[C:57](\[CH3:67])/[CH2:56][CH2:55]/[CH:54]=[C:53](\[CH3:68])/[CH2:52][CH2:51][CH:50]=[C:49]([CH3:69])[CH3:48])[C:63]([OH:65])=[O:64])=[O:14]

Participants

6

Reactant 4

HCID 18265-Hydroxyindoleacetic AcidHCID 81531DiisopropylethylamineHCID 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 46208950(R)-2-(2-(5-hydroxy-1H-indol-3-yl)acetamido)-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)propanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 24 mL vial, 5-hydroxyl indole-3-acetic acid (191 mg, 1.0 mmol), HATU (380 mg, 1 mmol) and N,N-diisopropyl-ethyl-amine (650 mg, 5 mmol) were mixed in THF (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. THF was removed by rotary evaporation. The resulting residue was dissolved in ethyl acetate (50 mL). The organic solution was washed with water (50 mL) and brain (50 mL), dried over Na2SO4, and concentrated to afford a crude mixture. The crude mixture was purified by preparative HPLC (210 mg, 42%) to yield Compound J. 1H-NMR (500 MHz, CD3OD): δ 1.49 (s, 9H), 1.56 (S, 3H), 1.85-1.98 (m, 6H), 2.62 (dd, J=8.0, 14.0 Hz, 1H), 2.80 (dd, J=4.5, 14.0 Hz, 1H), 2.88 (dd, J=7.0, 13.0 Hz, 1H), 2.98 (dd, J=8.5, 13.0 Hz, 1H), 3.55 (dd, J=6.5, 22.5 Hz, 2H), 4.49 (dd, J=5.0, 8.0 Hz, 1H), 4.98 (bs, 2H), 6.57 (d, J=8.5 Hz, 1H), 6.84 (s, 1H), 7.07 (d, J=6.5 Hz, 2H). 13C-NMR (125 MHz, CD3OD): δ 16.2, 17.8, 26.0, 27.3, 27.4, 27.8, 28.8, 30.2, 33.3, 33.8, 40.7, 40.9, 53.4, 103.7, 108.2, 112.7, 112.8, 121.5, 125.2, 125.5, 125.8, 129.3, 132.1, 133.0, 136.2, 140.5, 151.5, 173.9, 174.9; ES-MS: mass calcd for Chemical Formula: C28H38N2O4S 498.3 (M+). Found (M+1) m/z 499.2.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customTHF was removed by rotary evaporation
  3. dissolutionThe resulting residue was dissolved in ethyl acetate (50 mL)
  4. washThe organic solution was washed with water (50 mL) and brain (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a crude mixture
  8. customThe crude mixture was purified by preparative HPLC (210 mg, 42%)

Sources & evidence

ORD record
ord-2d54287c7e7e44e8858867d3dc8063d6
Source dataset
uspto-grants-2016_08
Patent number
US09415026B2

Linked notes

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