Hydrochloric Acid → HCID 86659023, compound

HRID 1471172Notes

Reaction equation

HRID 1471172 reaction equation
[ClH:1].C(OC([N:9]1[C@H:14]([C:15]2[NH:16][C:17]([C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[CH:26]=[C:25]([C:30]3[CH:35]=[CH:34][C:33]([C:36]5[NH:40][C:39]([C@@H:41]6[CH2:46][C@@H:45]7[C@@H:43]([CH2:44]7)[N:42]6[C:47]([O:49][CH2:50][C:51]6[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=6)=[O:48])=[N:38][CH:37]=5)=[CH:32][CH:31]=3)[CH:24]=[CH:23]4)=[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:16][C:17]([C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[CH:26]=[C:25]([C:30]3[CH:31]=[CH:32][C:33]([C:36]5[NH:40][C:39]([C@@H:41]6[CH2:46][C@@H:45]7[C@@H:43]([CH2:44]7)[N:42]6[C:47]([O:49][CH2:50][C:51]6[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=6)=[O:48])=[N:38][CH:37]=5)=[CH:34][CH:35]=3)[CH:24]=[CH:23]4)=[CH:18][N:19]=1)[NH:9]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86659024HCID 86659024, compound

Product 2

HCID 313Hydrochloric AcidHCID 86659023HCID 86659023, compoundYield 118.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 4.0 M HCl (1.167 mL, 4.67 mmol) in dioxane was added to a stirred solution of (1R,3S,5R)-benzyl 3-(5-(4-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (228 mg, 0.311 mmol) in dioxane (3 mL) and the reaction was stirred vigorously at rt for 3 h. The reaction was concentrated to yield an HCl salt of (1R,3S,5R)-benzyl 3-(5-(4-(6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (233 mg) as a yellow solid. LC-MS retention time 3.988 min; m/z 633.18 (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 1 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) δ ppm 8.44 (s, 1 H), 8.28 (s, 1 H), 8.08-8.18 (m, 3 H), 7.92-8.02 (m, 4 H), 7.84 (br. s., 3 H), 7.31 (br. s., 5 H), 5.21 (d, J=12.1, 1 H), 4.95-5.05 (m, 2 H), 4.80-4.91 (m, 1 H), 3.70-3.77 (m, 1 H), 3.59-3.67 (m, 1 H), 2.77-2.93 (m, 2 H), 2.74 (dd, J=13.4, 9.2 Hz, 1 H), 2.46 (dt, J=13.5, 6.7 Hz, 1 H), 2.12-2.22 (m, 1 H), 1.83-1.96 (m, 1 H), 1.27-1.35 (m, 1 H), 1.09 (q, J=7.9 Hz, 1 H), 0.95 (ddd, J=8.7, 5.9, 5.8 Hz, 1 H), 0.75-0.83 (m, 1 H).

Workup

  1. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-867e80cf81674f10b51d10435b58441d
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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