Hydrochloric Acid → HCID 178419972, compound

HRID 1471178Notes

Reaction equation

HRID 1471178 reaction equation
[ClH:1].C(OC([N:9]1[C@H:14]([C:15]2[NH:16][CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4[CH:27]=[C:28]5[C:33](=[CH:34][CH:35]=4)[N:32]=[C:31]([C:36]4[N:37]=[C:38]([C@@H:41]6[CH2:46][C@@H:45]7[C@@H:43]([CH2:44]7)[N:42]6C(OC(C)(C)C)=O)[NH:39][CH:40]=4)[CH:30]=[CH:29]5)=[CH:22][CH:21]=3)[N:19]=2)[CH2:13][C@@H:12]2[C@H:10]1[CH2:11]2)=O)(C)(C)C>O1CCOCC1.CO.C(Cl)Cl>[ClH:1].[C@@H:43]12[CH2:44][C@@H:45]1[CH2:46][C@@H:41]([C:38]1[NH:39][CH:40]=[C:36]([C:31]3[CH:30]=[CH:29][C:28]4[C:33](=[CH:34][CH:35]=[C:26]([C:23]5[CH:24]=[CH:25][C:20]([C:18]6[N:19]=[C:15]([C@@H:14]7[CH2:13][C@@H:12]8[C@@H:10]([CH2:11]8)[NH:9]7)[NH:16][CH:17]=6)=[CH:21][CH:22]=5)[CH:27]=4)[N:32]=3)[N:37]=1)[NH:42]2

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 178452523HCID 178452523, compound

Product 2

HCID 313Hydrochloric AcidHCID 178419972HCID 178419972, compoundYield 150.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 4M HCl (1 mL, 4.00 mmol) in dioxane was added to a suspension of tert-butyl(1R,3S,5R)-3-(4-(6-(4-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)phenyl)-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (130 mg, 0.186 mmol) in dioxane (3 mL), MeOH (0.5 mL) and DCM (3 mL) and the mixture was stirred at rt for 2 h. The reaction was concentrated to yield an HCl salt of 2-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)-6-(4-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)phenyl)quinoline (140 mg) as yellow solid. LC-MS retention time 2.063 min; m/z 500.37 (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), 8.56-8.62 (m, 2 H), 8.47-8.53 (m, 2 H), 8.07 (s, 1 H), 8.02-8.06 (m, 4 H), 4.97 (dd, J=10.8, 8.0 Hz, 1 H), 3.65-3.71 (m, 1 H), 3.55-3.65 (m, 2 H), 2.73-2.86 (m, 3 H), 2.61-2.72 (m, 1 H), 2.07-2.20 (m, 2 H), 1.25-1.35 (m, 2 H), 1.07 (t, 2 H).

Workup

  1. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-2c8f44b5013349cdbd0dbad899e9ac24
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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