Trifluoroacetic acid → HCID 178419971, compound

HRID 1471129Notes

Reaction equation

HRID 1471129 reaction equation
C(OC([N:8]1[C@H:13]([C:14]2[NH:15][C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[CH:25]=[C:24]([C:29]3[CH:34]=[CH:33][C:32]([C:35]5[NH:39][C:38]([C@@H:40]6[CH2:45][C@@H:44]7[C@@H:42]([CH2:43]7)[N:41]6C(OC(C)(C)C)=O)=[N:37][CH:36]=5)=[CH:31][CH:30]=3)[CH:23]=[CH:22]4)=[CH:17][N:18]=2)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=O)(C)(C)C.[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]>C(Cl)Cl>[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54].[C@@H:9]12[CH2:10][C@@H:11]1[CH2:12][C@@H:13]([C:14]1[NH:18][CH:17]=[C:16]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[CH:25]=[C:24]([C:29]3[CH:34]=[CH:33][C:32]([C:35]5[N:39]=[C:38]([C@@H:40]6[CH2:45][C@@H:44]7[C@@H:42]([CH2:43]7)[NH:41]6)[NH:37][CH:36]=5)=[CH:31][CH:30]=3)[CH:23]=[CH:22]4)[N:15]=1)[NH:8]2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66982182HCID 66982182, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178419971HCID 178419971, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1R,3S,5R)-tert-butyl 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 (275 mg) in DCM (10 mL) was added TFA (2 mL, 26.0 mmol). The mixture was stirred for 2 h at room temperature. The volatiles were removed under vacuum and the crude residue was purified by a reverse phase HPLC (water/MeOH/TFA) to afford a TFA salt of (1R,3S,5R)-3-(4-(4-(6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)-2-naphthyl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (106 mg) as tan solid. LC-MS retention time 1.153 min; m/z 499.36 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×30 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 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% TFA and Solvent B was 10% H2O/90% MeOH/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 8.33 (s, 1H), 8.19 (s, 1H), 7.99-8.05 (m, 2H), 7.85-7.95 (m, 6H), 7.83 (s, 1H), 7.76 (s, 1H), 4.78 (q, J=9.4 Hz, 2H), 3.47-3.54 (m, 2H), 2.65-2.74 (m, 4H), 2.02-2.12 (m, 2H), 1.18-1.25 (m, 2H), 0.97-1.05 (m, 2H).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe crude residue was purified by a reverse phase HPLC (water/MeOH/TFA)

Sources & evidence

ORD record
ord-3a45ed03476d46128633a977dd95ed87
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

Loading…