Hydrochloric Acid → HCID 57920106, compound

HRID 19400Notes

Reaction equation

HRID 19400 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:35])[C@@H:9]([N:14]1[CH2:18][C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C@H:27]3[CH2:31][O:30]C(C)(C)[O:28]3)=[CH:22][CH:21]=2)=[CH:16][C:15]1=[O:34])[CH2:10][CH:11]([CH3:13])[CH3:12].Cl>O1CCCC1>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:35])[C@@H:9]([N:14]1[CH2:18][C:17]([O:19][C:20]2[CH:21]=[CH:22][C:23]([CH2:26][C@H:27]([OH:28])[CH2:31][OH:30])=[CH:24][CH:25]=2)=[CH:16][C:15]1=[O:34])[CH2:10][CH:11]([CH3:13])[CH3:12]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66895137HCID 66895137, compound

Product 1

HCID 57920106HCID 57920106, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-2-{4-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid pyrazin-2-ylamide (0.025, 0.05 mmol) in tetrahydrofuran (5 mL) was treated with 1 M hydrochloric acid (1 mL) and stirred at room temperature overnight. The resulting mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous phase made basic (pH=8) by the addition of a 1N aqueous sodium hydroxide and extracted with ethyl acetate. The combined organic layers were concentrated in vacuo and the residue purified by flash column chromatography (silica gel 0% to 20% tetrahydrofuran/ethyl acetate) to afford (S)-2-{4-[4-((S)-2,3-dihydroxy-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid pyrazin-2-ylamide (15 mg, 65%) as a white solid: HR-ES-MS m/z calculated for C23H28N4O5 [M+H]+ 441.2133, observed 441.2132; 1H NMR (300 MHz, CDCl3) δ ppm 1.05 (d, J=6.4 Hz, 3H), 1.10 (d, J=6.4 Hz, 3H), 1.43-1.82 (m, 2H), 1.85-2.00 (m, 1H), 2.62 (dd, J=13.0, 11.2 Hz, 1H), 2.85 (d, J=13.9 Hz, 1H), 3.35 (br. s., 2H), 3.61-3.84 (m, 2H), 3.94-4.16 (m, 2H), 4.31 (d, J=18.1 Hz, 1H), 4.78-4.87 (m, 1H), 4.87 (br. s., 1H), 7.01 (d, J=8.2 Hz, 2H), 7.24-7.27 (m, 2H), 8.26 (s, 1H), 8.38 (s, 1H), 9.62 (s, 1H), 10.27 (br. s., 1H).

Workup

  1. customThe resulting mixture was partitioned between ethyl acetate and water
  2. customThe layers were separated
  3. additionby the addition of a 1N aqueous sodium hydroxide
  4. extractionextracted with ethyl acetate
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customthe residue purified by flash column chromatography (silica gel 0% to 20% tetrahydrofuran/ethyl acetate)

Sources & evidence

ORD record
ord-15026c643a1041b584e1d660efd41bf2
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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