Hydrochloric Acid → HCID 57920111, compound

HRID 19170Notes

Reaction equation

HRID 19170 reaction equation
CC1(C)[O:6][C@@H:5]([C:7]2[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][CH3:34])[C:27]=4[F:35])=[CH:22][C:21]3=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:11][CH:12]=2)[CH2:4][O:3]1.Cl>O1CCCC1.C(OCC)(=O)C>[OH:6][C@@H:5]([C:7]1[N:8]=[CH:9][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:33][CH3:34])[C:27]=3[F:35])=[CH:22][C:21]2=[O:36])[CH2:16][CH:17]([CH3:18])[CH3:19])=[N:11][CH:12]=1)[CH2:4][OH:3]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57920025HCID 57920025, compound

Product 1

HCID 57920111HCID 57920111, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-yl]-amide (prepared in Example 150, 0.300 g, 0.57 mmol) in tetrahydrofuran (20 mL) was treated with 1N aqueous hydrochloric acid (10 mL). The reaction mixture was stirred for 20 h at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate, a saturated sodium chloride solution and dried over magnesium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 10% to 100% (9:1 dichloromethane:methanol)/hexanes) to afford (S)-2-[4-(3-ethoxy-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [5-((S)-1,2-dihydroxy-ethyl)-pyrazin-2-yl]-amide (0.188 g, 68%) as a fluffy white solid: HR-ES-MS m/z calculated for C24H29FN4O6, [M+H]+ 489.2144 observed 489.2143; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.92 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 1.36 (t, J=6.9 Hz, 3H), 1.42-1.57 (m, 1H), 1.57-1.73 (m, 1H), 1.74-1.90 (m, 1H), 3.47-3.61 (m, 1H), 3.68 (dt, J=10.8, 5.3 Hz, 1H), 4.15 (q, J=6.9 Hz, 2H), 4.26 (d, J=18.4 Hz, 1H), 4.53-4.68 (m, 2H), 4.73 (t, J=5.7 Hz, 1H), 4.92 (s, 1H), 5.03 (dd, J=10.6, 4.2 Hz, 1H), 5.55 (d, J=4.8 Hz, 1H), 6.98-7.08 (m, 1H), 7.08-7.25 (m, 2H), 8.45 (s, 1H), 9.17 (s, 1H), 11.15 (s, 1H).

Workup

  1. washwashed with saturated sodium bicarbonate
  2. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  3. customThe solvents were evaporated
  4. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; 10% to 100% (9:1 dichloromethane:methanol)/hexanes)

Sources & evidence

ORD record
ord-15ebff60fcfa4ecd949299c6e1345f42
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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