Hydrochloric Acid → HCID 178419970, compound

HRID 1471180Notes

Reaction equation

HRID 1471180 reaction equation
[ClH:1].C(OC([N:9]1[C@H:14]([C:15]2[NH:16][C:17]([C:20]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:21]=3[CH:22]=[CH:23][CH:24]=[C:25]4[C:30]3[CH:35]=[CH:34][C:33]([C:36]4[NH:40][C:39]([C@@H:41]5[CH2:46][C@@H:45]6[C@@H:43]([CH2:44]6)[N:42]5C(OC(C)(C)C)=O)=[N:38][CH:37]=4)=[CH:32][CH:31]=3)=[CH:18][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:19][CH:18]=[C:17]([C:20]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:21]=3[CH:22]=[CH:23][CH:24]=[C:25]4[C:30]3[CH:31]=[CH:32][C:33]([C:36]4[NH:40][C:39]([C@@H:41]5[CH2:46][C@@H:45]6[C@@H:43]([CH2:44]6)[NH:42]5)=[N:38][CH:37]=4)=[CH:34][CH:35]=3)[N:16]=1)[NH:9]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58498993HCID 58498993, compound

Product 2

HCID 313Hydrochloric AcidHCID 178419970HCID 178419970, compoundYield 118.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4M HCl (0.757 mL, 3.03 mmol) in dioxane was added to a solution of (1R,3S,5R)-tert-butyl 3-(5-(4-(5-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-1-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (141 mg, 0.202 mmol) in dioxane (3.0 mL) and the reaction was stirred at rt for 6 h. The solids were washed down the sides of the vial with MeOH and the reaction was concentrated under a stream nitrogen to yield an HCl salt of (1R,3S,5R)-3-(5-(4-(5-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-4-yl)naphthalen-1-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (119 mg) as a yellow solid. LC-MS retention time 2.333 min; m/z 499.57 (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 8.15 (d, J=8.3 Hz, 1 H), 8.03-8.08 (m, 2 H), 8.01 (d, J=8.0 Hz, 2 H), 7.95 (s, 1 H), 7.77 (d, J=6.5 Hz, 1 H), 7.68-7.74 (m, 1 H), 7.65 (d, J=8.0 Hz, 2 H), 7.57-7.64 (m, 2 H), 5.03 (t, J=9.4 Hz, 1 H), 4.97 (dd, J=10.8, 8.0 Hz, 1 H), 3.57-3.66 (m, 2 H), 2.76-2.89 (m, 4 H), 2.11-2.21 (m, 2 H), 1.27-1.34 (m, J=7.7, 5.1, 5.1, 2.6 Hz, 2 H), 1.05-1.14 (m, 2 H).

Workup

  1. washThe solids were washed down the sides of the vial with MeOH
  2. concentrationthe reaction was concentrated under a stream nitrogen

Sources & evidence

ORD record
ord-17cec1a7a9384f5f8ad302df34741e87
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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