Hydrochloric Acid → (S)-3-cyclopentyl-N-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1261505Notes

Reaction equation

HRID 1261505 reaction equation
[CH:1]1([CH2:6][C@H:7]([N:24]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][C:30]=3[C:33]([F:36])([F:35])[F:34])[C:25]2=[O:37])[C:8]([NH:10][C:11]2[CH:16]=[N:15][C:14]([C@H:17]3[CH2:21][O:20]C(C)(C)[O:18]3)=[CH:13][N:12]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH:1]1([CH2:6][C@H:7]([N:24]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][C:30]=3[C:33]([F:35])([F:36])[F:34])[C:25]2=[O:37])[C:8]([NH:10][C:11]2[CH:16]=[N:15][C:14]([C@H:17]([OH:18])[CH2:21][OH:20])=[CH:13][N:12]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 70945613(S)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide

Product 1

HCID 70674684(S)-3-cyclopentyl-N-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamideYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-3-cyclopentyl-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide (74 mg, 0.14 mmol) in tetrahydrofuran (1.5 mL) was treated with a 1N aqueous hydrochloric acid solution (1.5 mL) and stirred at room temperature until there was no more starting material as indicated by TLC (overnight, ˜16 h). After this time, the reaction was treated with a saturated aqueous sodium bicarbonate solution and then extracted with ethyl acetate (3×20 mL). The organic layers were then combined and dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo. The crude material was purified using an Analogix Intelliflash 280 chromatography system (4 g silica gel column, 100% ethyl acetate) to afford (S)-3-cyclopentyl-N-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide (49 mg, 72%) as a white foam: [α]28D=−41.6° (c=0.25, methylene chloride); HR-ES(+) m/e calcd for C23H25N4O4F3 [M+H]+ 479.1901, observed 479.1899; 1H NMR (300 MHz, DMSO-d6) δ 11.27 (s, 1H), 9.16 (s, 1H), 8.45 (d, J=0.91 Hz, 1H), 8.02 (t, J=8.45 Hz, 2H), 7.70-7.82 (m, 1H), 5.55 (br. s., 1H), 5.22 (dd, J=5.13, 10.26 Hz, 1H), 5.05 (d, J=18.11 Hz, 1H), 4.90-4.50 (br. s., 1H), 4.75 (d, J=18.11 Hz, 1H), 4.62 (t, J=5.13 Hz, 1H), 3.61-3.72 (m, 1H), 3.49-3.60 (m, 1H), 1.03-2.21 (m, 11H).

Workup

  1. customas indicated by TLC (overnight, ˜16 h)
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customto remove the drying agent
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe crude material was purified

Sources & evidence

ORD record
ord-23c18ec1e5b6473b8161593ab0391d2c
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

Loading…