Hydrochloric Acid → (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide

HRID 1261514Notes

Reaction equation

HRID 1261514 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][CH:17]([CH3:19])[CH3:18])=[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][CH:17]([CH3:19])[CH3:18])=[N:11][CH:12]=1)[CH2:4][OH:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86673402(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide

Product 1

HCID 70674680(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amideYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide (53 mg, 0.11 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)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide (43 mg, 88%) as a cream colored foam: [α]29D=+22.9° (c=0.14, methanol); HR-ES(+) m/e calcd for C21H23N4O4F3 [M+H]+ 453.1744, observed 453.1744; 1H NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H), 9.16 (s, 1H), 8.45 (d, J=1.07 Hz, 1H), 8.02 (dd, J=7.67, 11.29 Hz, 2H), 7.67-7.85 (m, 1H), 5.55 (d, J=4.90 Hz, 1H), 5.28 (dd, J=5.11, 10.65 Hz, 1H), 5.05 (d, J=18.33 Hz, 1H), 4.66-4.78 (m, 2H), 4.62 (q, J=4.90 Hz, 1H), 3.67 (td, J=5.30, 10.92 Hz, 1H), 3.55 (td, J=5.78, 11.24 Hz, 1H), 1.95-2.09 (m, 1H), 1.71-1.88 (m, 1H), 1.49 (br. s., 1H), 0.90-1.00 (m, 6H).

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-f15e9d97453740b6834ac70f276e971f
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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