Hydrochloric Acid → HCID 178437182, compound

HRID 625620Notes

Reaction equation

HRID 625620 reaction equation
[ClH:1].C(OC([N:9]1[C@H:14]([C:15]2[NH:16][CH:17]=[C:18]([C:20]#[C:21][C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[CH:28]=[C:27]([C:32]3[N:33]=[C:34]([C@@H:37]5[CH2:42][C@@H:41]6[C@@H:39]([CH2:40]6)[N:38]5C(OC(C)(C)C)=O)[NH:35][CH:36]=3)[CH:26]=[CH:25]4)[N:19]=2)[CH2:13][C@@H:12]2[C@H:10]1[CH2:11]2)=O)(C)(C)C>O1CCOCC1>[ClH:1].[C@@H:10]12[CH2:11][C@@H:12]1[CH2:13][C@@H:14]([C:15]1[NH:16][CH:17]=[C:18]([C:20]#[C:21][C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[CH:28]=[C:27]([C:32]3[NH:33][C:34]([C@@H:37]5[CH2:42][C@@H:41]6[C@@H:39]([CH2:40]6)[NH:38]5)=[N:35][CH:36]=3)[CH:26]=[CH:25]4)[N:19]=1)[NH:9]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 178452529HCID 178452529, compound

Product 2

HCID 313Hydrochloric AcidHCID 178437182HCID 178437182, compoundYield 128.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4M HCl (1.546 mL, 6.18 mmol) in dioxane was added to a solution of tert-butyl (1R,3S,5R)-3-(4-(6-((2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)ethynyl)-2-naphthyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (200 mg, 0.309 mmol) in dioxane (3 mL) and the reaction was vigorously stirred for 4 h. The reaction slurry was concentrated to yield an HCl salt of (1R,3S,5R)-3-(5-(6-((2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-4-yl)ethynyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (177 mg) as a yellow solid. LC-MS retention time 3.403 min; m/z 893.29 (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 5% MeOH/95% H2O/10 mM ammonium acetate and Solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) d ppm 8.42 (s, 1H), 8.16 (s, 2H), 8.05 (d, J=8.8 Hz, 1H), 8.03 (d, J=8.8 Hz, 1H), 7.97 (dd, J=8.8, 1.8 Hz, 1H), 7.74 (s, 1H), 7.66 (dd, J=8.5, 1.5 Hz, 1H), 5.01 (dd, J=10.8, 7.8 Hz, 1H), 4.78 (dd, J=10.8, 8.3 Hz, 1H), 3.57-3.77 (m, 2H), 3.50-3.56 (m, 1H), 2.61-2.92 (m, 4H), 2.13-2.21 (m, 1H), 2.06-2.13 (m, 1H), 1.25 (ddd, J=7.8, 5.0, 2.5 Hz, 1H), 0.99-1.14 (m, 2H).

Workup

  1. concentrationThe reaction slurry was concentrated

Sources & evidence

ORD record
ord-28de4094a69a4de89242899f37346f3c
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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