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

HRID 1261509Notes

Reaction equation

HRID 1261509 reaction equation
CC1(C)[O:6][C@@H:5]([C:7]2[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:34])[C@@H:15]([N:20]3[CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[C:29]([F:32])([F:31])[F:30])[C:21]3=[O:33])[CH2:16][CH2:17][S:18][CH3:19])=[N:11][CH:12]=2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([C:7]1[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:34])[C@@H:15]([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][C:26]=3[C:29]([F:32])([F:30])[F:31])[C:21]2=[O:33])[CH2:16][CH2:17][S:18][CH3:19])=[N:11][CH:12]=1)[CH2:4][OH:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 70945445(S)-N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyramide

Product 1

HCID 70674571(S)-N-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyramideYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)—N-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyramide (26 mg, 0.05 mmol) in tetrahydrofuran (1 mL) was treated with a 1N aqueous hydrochloric acid solution (1 mL) and stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to remove the tetrahydrofuran and the remaining material was partitioned between ethyl acetate and a saturated aqueous sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate, filtered to remove the drying agent and the filtrate concentrated in vacuo to afford (S)—N-[5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyramide (20 mg, 85%) as a pale yellow gum: HR-ES(+) m/e calcd for C20H21N4O4SF3 [M+H]+ 471.1309, observed 471.1306; 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 9.16 (s, 1H), 8.44 (d, J=1.28 Hz, 1H), 8.02 (t, J=7.46 Hz, 2H), 7.71-7.81 (m, 1H), 5.55 (d, J=4.90 Hz, 1H), 5.18 (dd, J=5.01, 9.48 Hz, 1H), 4.93-5.02 (m, 1H), 4.77-4.87 (m, 1H), 4.72 (t, J=5.86 Hz, 1H), 4.58-4.66 (m, 1H), 3.61-3.71 (m, 1H), 3.55 (td, J=5.86, 11.29 Hz, 1H), 2.48-2.65 (m, 3H), 2.22-2.38 (m, 1H), 2.09 (s, 3H).

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customto remove the tetrahydrofuran
  3. customthe remaining material was partitioned between ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customto remove the drying agent
  8. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-a1c936669b9447b489f3b892d86be3e3
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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