Hydrochloric Acid → HCID 57920156, compound

HRID 19387Notes

Reaction equation

HRID 19387 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[CH:34]=[CH:33][CH:32]=[C:31]5[C:27]=4[CH:28]=[N:29][N:30]5[CH3:35])=[CH:22][C:21]3=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl.C(OCC)(=O)C.[OH-].[Na+]>O1CCCC1.O>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:37])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[CH:28]=[N:29][N:30]4[CH3:35])=[CH:22][C:21]2=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 86635243(S)-4-Methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 57920156HCID 57920156, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-4-methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (0.025 g, 0.05 mmol) in tetrahydrofuran (5 mL) was treated with 1M aqueous hydrochloric acid (1 mL) and the resulting mixture was stirred at room temperature overnight. The mixture was partioned between ethyl acetate and water. The aqueous phase was made basic with 1N aqueous sodium hydroxide and extracted with ethyl acetate twice. The combined organic phase was concentrated in vacuo and the residue purified by flash column chromatography (silica gel, 0% to 40% tetrahydrofuran/ethyl acetate) which afforded (S)-4-methyl-2-[4-(1-methyl-1H-indazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (0.013 g, 56%) as a white solid: HR-ES-MS m/z calculated for C24H30N6O5 [M+H]+ 483.2351, observed 483.235; 1H NMR (300 MHz, CDCl3) δ ppm 0.97 (d, J=6.6 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H), 1.59 (br. s., 1H), 1.69-1.97 (m, 2H), 2.72 (br. s., 2H), 3.56 (dd, J=11.8, 4.8 Hz, 1H), 3.68 (dd, J=11.8, 3.3 Hz, 1H), 4.06-4.16 (m, 5H), 4.20 (d, J=18.4 Hz, 1H), 4.48 (d, J=18.4 Hz, 1H), 4.88 (t, J=7.8 Hz, 1H), 5.03 (s, 1H), 6.66 (d, J=2.1 Hz, 1H), 6.94 (d, J=7.2 Hz, 1H), 7.29-7.43 (m, 4H), 7.96 (s, 1H), 9.39 (br. s., 1H).

Workup

  1. extractionextracted with ethyl acetate twice
  2. concentrationThe combined organic phase was concentrated in vacuo
  3. customthe residue purified by flash column chromatography (silica gel, 0% to 40% tetrahydrofuran/ethyl acetate) which

Sources & evidence

ORD record
ord-50633dc17cce48078bbf0229a0128a0f
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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