Hydrochloric Acid → (S)-3-cyclohexyl-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide

HRID 1925926Notes

Reaction equation

HRID 1925926 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:25]2[CH2:29][C:28]3[CH2:30][C:31]4[C:32]([O:38][CH3:39])=[CH:33][CH:34]=[CH:35][C:36]=4[O:37][C:27]=3[C:26]2=[O:40])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH2:17][C@@H:18]3[CH2:22][O:21]C(C)(C)[O:19]3)[N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>O1CCCC1>[CH:1]1([CH2:7][C@H:8]([N:25]2[CH2:29][C:28]3[CH2:30][C:31]4[C:32]([O:38][CH3:39])=[CH:33][CH:34]=[CH:35][C:36]=4[O:37][C:27]=3[C:26]2=[O:40])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH2:17][C@@H:18]([OH:19])[CH2:22][OH:21])[N:13]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67520957(S)-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide

Product 1

HCID 54765735(S)-3-cyclohexyl-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

A solution of (S)-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (140 mg, 0.25 mmol) in tetrahydrofuran (5 mL) was treated with 2N HCl (2.05 mL, 0.31 mmol). The mixture was stirred for 4 hours at 23° C. The reaction mixture after aqueous work-up and silica gel flash chromatography using hexane-ethyl acetate gradient elution, afforded (S)-3-cyclohexyl-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-2-(8-methoxy-3-oxo-3,9-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-propionamide (68.1 mg, 52.7%), as a white solid. 1H NMR (DMSO-d6) δ: 10.80 (s, 1H), 7.52 (s, 1H), 7.22 (t, J=8.3 Hz, 1H), 6.76 (d, J=8.3 Hz, 1H), 6.68 (d, J=8.3 Hz, 1H), 6.39 (s, 1H), 4.93 (d, J=4.9 Hz, 2H), 4.70 (br. s., 1H), 4.37 (d, J=19.1 Hz, 1H), 4.09 (dd, J=13.4, 4.2 Hz, 1H), 3.99 (d, J=19.1 Hz, 2H), 3.88 (d, J=7.8 Hz, 1H), 3.83-3.86 (m, 1H), 3.76 (br. s., 2H), 3.53 (s, 3H), 1.50-1.83 (m, 7H), 0.81-1.31 (m, 6H).

Workup

  1. washhexane-ethyl acetate gradient elution

Sources & evidence

ORD record
ord-2293502c3c8649b8bd1717f434fb8252
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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