Hydrochloric Acid → HCID 178461187, compound

HRID 1471185Notes

Reaction equation

HRID 1471185 reaction equation
[ClH:1].C(O)(C(F)(F)F)=O.C(OC([N:16]1[C@@H:20]([CH3:21])[CH2:19][CH2:18][C@H:17]1[C:22]1[NH:23][C:24]([C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[CH:33]=[C:32]([C:37]#[C:38][C:39]2[NH:43][C:42]([C@@H:44]4[CH2:49][C@@H:48]5[C@@H:46]([CH2:47]5)[N:45]4C(OC(C)(C)C)=O)=[N:41][CH:40]=2)[CH:31]=[CH:30]3)=[CH:25][N:26]=1)=O)(C)(C)C>O1CCOCC1>[ClH:1].[CH3:21][C@@H:20]1[NH:16][C@H:17]([C:22]2[NH:26][CH:25]=[C:24]([C:27]3[CH:28]=[C:29]4[C:34](=[CH:35][CH:36]=3)[CH:33]=[C:32]([C:37]#[C:38][C:39]3[N:43]=[C:42]([C@@H:44]5[CH2:49][C@@H:48]6[C@@H:46]([CH2:47]6)[NH:45]5)[NH:41][CH:40]=3)[CH:31]=[CH:30]4)[N:23]=2)[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 58498714HCID 58498714, compound

Product 2

HCID 313Hydrochloric AcidHCID 178461187HCID 178461187, compoundYield 135.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4M HCl (0.611 mL, 2.445 mmol) in dioxane was added to a mixture of a TFA salt of (1R,3S,5R)-tert-butyl 3-(5-((6-(2-((2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (53.6 mg, 0.061 mmol) in dioxane (1.5 mL) and the reaction was vigorously stirred for 2 h. The reaction was concentrated under a steam of nitrogen overnight to yield an HCl salt of (1R,3S,5R)-3-(4-((6-(2-((2S,5S)-5-methylpyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (37 mg) which was used without further purification. LC-MS retention time 2.302 min; m/z 449.40 (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.

Workup

  1. concentrationThe reaction was concentrated under a steam of nitrogen overnight

Sources & evidence

ORD record
ord-848a3ddb0fe9406d9c03b1afbd0056d3
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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