Trifluoroacetic acid → HCID 178419930, compound

HRID 1471145Notes

Reaction equation

HRID 1471145 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C(OC([N:15]1[C@@H:20]([C:21]2[NH:22][CH:23]=[C:24]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[CH:32]=[C:31]([C:36]3[CH:37]=[C:38]([C:42]5[N:43]=[C:44]([C@@H:47]6[CH2:52][C@@H:51]7[C@@H:49]([CH2:50]7)[N:48]6C(OC(C)(C)C)=O)[NH:45][CH:46]=5)[CH:39]=[CH:40][CH:41]=3)[CH:30]=[CH:29]4)[N:25]=2)[CH2:19][C@H:18]2[C@@H:16]1[CH2:17]2)=O)(C)(C)C>C(Cl)Cl>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[C@H:16]12[CH2:17][C@H:18]1[CH2:19][C@H:20]([C:21]1[NH:22][CH:23]=[C:24]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[CH:32]=[C:31]([C:36]3[CH:37]=[C:38]([C:42]5[N:43]=[C:44]([C@@H:47]6[CH2:52][C@@H:51]7[C@@H:49]([CH2:50]7)[NH:48]6)[NH:45][CH:46]=5)[CH:39]=[CH:40][CH:41]=3)[CH:30]=[CH:29]4)[N:25]=1)[NH:15]2

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178452525HCID 178452525, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178419930HCID 178419930, compoundYield 103.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 26.0 mmol) was added to a solution of tert-butyl(1R,3S,5R)-3-(4-(3-(6-(2-((1S,3R,5S)-2-(tert-butoxycarbonyl)-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-2-carboxylate (130 mg, 0.20 mmol) in DCM (2 mL) and the mixture was stirred for 2 h at RT. The volatiles were removed under vacuum and the crude product was purified by prep HPLC (methanol/water, 0.1% TFA) to yield a TFA salt of (1R,3S,5R)-3-(4-(3-(6-(2-((1S,3R,5S)-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 (103 mg) as a tan solid. LC-MS retention time 1.303 min; m/z 499.13 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire C18 4.6×30 mm 5 μM 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% methanol/90% water/0.1% TFA and Solvent B was 10% water/90% methanol/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), 8.22 (d, J=12.5 Hz, 2H), 8.02 (dd, J=8.6, 5.8 Hz, 2H), 7.90-7.97 (m, 2H), 7.75-7.82 (m, 4H), 7.58 (t, J=7.8 Hz, 1H), 4.74-4.78 (m, 2H), 3.46-3.53 (m, 2H), 2.64-2.74 (m, 4H), 2.04-2.12 (m, 2H), 1.19-1.26 (m, 2H), 1.02 (ddd, J=14.2, 7.3, 7.2 Hz, 2H).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe crude product was purified by prep HPLC (methanol/water, 0.1% TFA)

Sources & evidence

ORD record
ord-b67c923561a7400d8d7f585a416152fb
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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