Trifluoroacetic acid → HCID 178419309, compound

HRID 625633Notes

Reaction equation

HRID 625633 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([C:19]1[N:20]=[C:21]([C@@H:24]3[CH2:29][C@@H:28]4[C@@H:26]([CH2:27]4)[N:25]3C(OC(C)(C)C)=O)[NH:22][CH:23]=1)[CH:13]=[CH:12]2>ClCCCl>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([C:19]1[N:20]=[C:21]([C@@H:24]3[CH2:29][C@@H:28]4[C@@H:26]([CH2:27]4)[NH:25]3)[NH:22][CH:23]=1)[CH:13]=[CH:12]2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 58498751(1R,3S,5R)-tert-butyl 3-(4-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate2×

Product 2

HCID 6422Trifluoroacetic acidHCID 178419309HCID 178419309, compoundYield 166.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

TFA (1.028 mL, 13.34 mmol) was added to a solution of (1R,3S,5R)-tert-butyl 3-(4-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (Intermediate 120) (606 mg, 1.334 mmol) in DCE (20 mL) and reaction was stirred at rt for 2 h. Then additional TFA (1 mL) was added and the reaction was stirred at rt for 4 h. The reaction was concentrated to dryness and the crude brown oil was dissolved into diethyl ether and concentrated under vacuum (2×) to yield a TFA salt of (1R,3S,5R)-3-(4-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (786 mg) as a yellow solid. The material was used without further purification. LC-MS retention time 2.558 min; m/z 352.03, 354.05 (1:1) (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u C18 3.0×50 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 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 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, chloroform-d) δ ppm 10.55 (br. s., 1H), 8.02 (s, 1H), 7.93 (d, J=1.5 Hz, 1H), 7.72 (d, J=8.5 Hz, 1H), 7.65 (d, J=8.8 Hz. 1H), 7.59 (dd, J=8.8, 2.0 Hz, 1H), 7.52 (dd, J=8.7, 1.6 Hz, 1H), 7.44 (s, 1H), 5.10 (dd, J=11.8, 7.3 Hz, 1H), 3.49-3.54 (m, 1H), 2.94 (td, J=12.7, 4.6 Hz, 1H), 2.68 (dd, J=13.2, 7.2 Hz, 1H), 2.06-2.14 (m, 1H), 1.20-1.26 (m, 1H), 1.00-1.09 (m, 1H).

Workup

  1. stirringthe reaction was stirred at rt for 4 h
  2. concentrationThe reaction was concentrated to dryness
  3. dissolutionthe crude brown oil was dissolved into diethyl ether
  4. concentrationconcentrated under vacuum (2×)

Sources & evidence

ORD record
ord-b190330fbe9e4fa480971f93334400c6
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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