Hydrochloric Acid → HCID 86706093, compound

HRID 2176254Notes

Reaction equation

ClC(Cl)(Cl)C[O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:54])[C@@H:14]([NH:16][C:17](=[O:53])[C@@H:18]([O:22][C:23]([C:25]2(/[CH:31]=[CH:32]/[C:33]3[CH:42]=[C:41]4[C:36]([CH:37]=[CH:38][C:39]([C@H:43]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH3:44])=[N:40]4)=[CH:35][CH:34]=3)[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[O:24])[CH:19]([CH3:21])[CH3:20])[CH3:15])[NH:8]1)=[O:6].[OH-].[Na+].Cl>O1CCCC1>[C:49]([O:48][C:46]([NH:45][C@@H:43]([C:39]1[CH:38]=[CH:37][C:36]2[C:41](=[CH:42][C:33](/[CH:32]=[CH:31]/[C:25]3([C:23]([O:22][C@@H:18]([CH:19]([CH3:21])[CH3:20])[C:17]([NH:16][C@@H:14]([CH3:15])[C:13]([N:9]4[CH2:10][CH2:11][CH2:12][C@@H:7]([C:5]([OH:6])=[O:4])[NH:8]4)=[O:54])=[O:53])=[O:24])[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)=[CH:34][CH:35]=2)[N:40]=1)[CH3:44])=[O:47])([CH3:52])([CH3:50])[CH3:51]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of (S)-1-{(S)-2-[(S)-2-(2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-tetrahydro-pyran-2-carbonyloxy)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloroethyl ester (42 mg, 0.05 mmol) in tetrahydrofuran (2 mL) was stirred at 0° C. under nitrogen. An ice-cold aqueous solution of sodium hydroxide (0.1 M, 0.5 mL, 0.05 mmol) was added and the reaction mixture was stirred at 0° C. for 30 minutes. Additional sodium hydroxide solution (0.1 M, 1.0 mL, 0.1 mmol) was added and the reaction mixture was stirred at 0° C. for 1 h. Additional sodium hydroxide solution (0.1 M, 1.0 mL, 0.1 mmol) was added and the reaction mixture was stirred at 0° C. for 90 minutes. Cold hydrochloric acid (1 M) was added to acidify the mixture to pH 2 and the solvent was evaporated. The residue was co-evaporated with tetrahydrofuran/toluene (1:1, 3×) and the residue was triturated with diethyl ether (2×) and the resulting solid was dried to afford (S)-1-{(S)-2-[(S)-2-(2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-tetrahydro-pyran-2-carbonyloxy)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (0.05 mmol) as a yellow solid and as a 1:1 mixture of diastereoisomers which was used crude in the next reaction. LCMS (m/z) 710.3 [M+H], Tr=2.80 min.

Workup

stirringthe reaction mixture was stirred at 0° C. for 1 h
stirringthe reaction mixture was stirred at 0° C. for 90 minutes
customthe solvent was evaporated
customthe residue was triturated with diethyl ether (2×)
customthe resulting solid was dried

Sources & evidence

ORD record: ord-514317452938448fa6228ef40b9bd9dd
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062092B2

Reaction notes

Loading…