Hydrochloric Acid → Dorzagliatin

HRID 19003Notes

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:34])[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[Cl:32])=[CH:22][C:21]3=[O:33])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl.O>CC(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:34])[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[Cl:32])=[CH:22][C:21]2=[O:33])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of (S)-2-[4-(2-chloro-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 (1.00 g, 1.99 mmol) in 2-propanol (4 mL) was added 2N hydrochloric acid (4.00 mL, 8.00 mmol). The mixture was stirred for 2 h at 25° C. Water (4 mL) was added and the mixture was thoroughly extracted with methyl t-butyl ether (30 mL). The organic layer was separated and washed with 1N sodium hydroxide (20 mL) and then brine (20 mL). Concentration of the organic layer provided a white foam. The foam was chopped up with a spatula to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (890 mg, 96.7%) as an off-white solid: LR-ES-MS m/z calculated for C22H27ClN4O5 [M]+ 462, [M+H]+ observed 463.

Workup

extractionthe mixture was thoroughly extracted with methyl t-butyl ether (30 mL)
customThe organic layer was separated
washwashed with 1N sodium hydroxide (20 mL)
customConcentration of the organic layer provided a white foam

Sources & evidence

ORD record: ord-e30b2249018a4590b5a80e14af6e9915
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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