Hydrochloric Acid → HCID 44252018, compound

HRID 19021Notes

Reaction equation

HRID 19021 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:36])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH2:33][CH3:34])=[CH:22][C:21]3=[O:35])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1.C(OCC)(=O)C>[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:36])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH2:33][CH3:34])=[CH:22][C:21]2=[O:35])[CH2:16][CH:17]([CH3:18])[CH3:19])=[N:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57920177(S)-2-[4-(2-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 44252018HCID 44252018, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-2-[4-(2-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (prepared as in Example 83, 95 mg, 0.19 mmol) in tetrahydrofuran (20 mL) was treated with 2N aqueous hydrochloric acid (10 mL). The reaction mixture was stirred for 4 h at 25° C. The reaction mixture was diluted with ethyl acetate, washed with water, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated to afford (S)-2-[4-(2-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide as a fluffy material. This material was dissolved in dichloromethane (20 mL) and treated with hydrogen chloride in diethyl ether (1 M, 2 mL). Solvents were evaporated and the residue was triturated with diethyl ether. The mixture was filtered to give (S)-2-[4-(2-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide hydrochloride (51 mg, 61%) as a light yellow solid: HR-ES-MS m/z calculated for C24H32N4O6 [M+H]+ 473.2395, observed 473.2395; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.88 (d, J=6.4 Hz, 3H) 0.91 (d, J=6.4 Hz, 3H) 1.24 (t, J=6.9 Hz, 3H) 1.40 (br. s., 1H) 1.46-1.62 (m, 1H) 1.64-1.80 (m, 1H) 3.17-3.40 (m, 2H) 3.69-3.79 (m, 1H) 3.79-3.90 (m, 1H) 3.98-4.11 (m, 4H) 4.49 (d, J=18.4 Hz, 1H) 4.72 (s, 1H) 4.86 (dd, J=11.0, 4.7 Hz, 1H) 6.38 (d, J=2.1 Hz, 1H) 6.97 (t, J=7.1 Hz, 1H) 7.13-7.20 (m, 1H) 7.21-7.33 (m, 2H) 7.51 (d, J=2.1 Hz, 1H) 10.72 (s, 1H).

Workup

  1. washwashed with water
  2. dry with materiala saturated sodium chloride solution and dried over sodium sulfate
  3. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-99a227342be14e78abace88cc42d2d5a
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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