Hydrochloric Acid → Quinoline

HRID 1471193Notes

Reaction equation

HRID 1471193 reaction equation
[ClH:1].C(OC(N1[C@@H](C)CC[C@H]1C1NC(C2C=CC([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[N:32]=[C:31](C3NC([C@@H]5CC[C@H](C)N5C(OC(C)(C)C)=O)=NC=3)[CH:30]=[CH:29]4)=CC=2)=CN=1)=O)(C)(C)C>O1CCOCC1>[ClH:1].[N:32]1[C:33]2[C:28](=[CH:27][CH:26]=[CH:35][CH:34]=2)[CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66982311HCID 66982311, compound

Product 2

HCID 313Hydrochloric AcidHCID 7047QuinolineYield 778.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4M HCl (0.2 mL, 0.8 mmol) in dioxane was added to a solution of (2S,5S)-tert-butyl 2-(5-(6-(4-(2-((2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)quinolin-2-yl)-1H-imidazol-2-yl)-5-methylpyrrolidine-1-carboxylate (12.7 mg, 0.018 mmol) in dioxane (1 mL) and the mixture was stirred at rt for 3d. The reaction mixture was concentrated to yield a crude HCl salt of 2-(2-((2S,5S)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)-6-(4-(242S,5S)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)quinoline (18.1 mg) as yellow solid. LC-MS retention time 2.597 min; m/z 504.46 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) δ ppm 9.09 (d, J=9.0 Hz, 1 H), 8.66 (s, 1 H), 8.54-8.61 (m, 2 H), 8.51 (d, J=9.0 Hz, 1 H), 8.50 (d, J=8.8 Hz, 1 H), 8.00-8.08 (m, 4 H), 7.99 (s, 1 H), 5.14 (t, J=8.5 Hz, 1 H), 5.07 (t, J=8.0 Hz, 1 H), 3.90-4.04 (m, 2 H), 2.52-2.75 (m, 4 H), 2.39-2.53 (m, 2 H), 1.98-2.14 (m, 2 H), 1.59 (dd, J=9.7, 6.7 Hz, 6 H).

Workup

  1. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-7d06c4b711b149e3ac7c7717aa5154b7
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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