Trifluoroacetic acid → Trifluoroacetic acid

HRID 1471120Notes

Reaction equation

HRID 1471120 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C(OC([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[NH:21][CH:22]=[C:23]([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[CH:31]=[C:30]([C:35]2[CH:40]=[CH:39][C:38]([C:41]4[NH:45][C:44]([C@@H:46]5[CH2:50][CH2:49][CH2:48][N:47]5C(OC(C)(C)C)=O)=[N:43][CH:42]=4)=[CH:37][CH:36]=2)[CH:29]=[CH:28]3)[N:24]=1)=O)(C)(C)C>C(Cl)Cl>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[NH:47]1[CH2:48][CH2:49][CH2:50][C@H:46]1[C:44]1[NH:45][C:41]([C:38]2[CH:39]=[CH:40][C:35]([C:30]3[CH:29]=[CH:28][C:27]4[C:32](=[CH:33][CH:34]=[C:25]([C:23]5[NH:24][C:20]([C@@H:16]6[CH2:17][CH2:18][CH2:19][NH:15]6)=[N:21][CH:22]=5)[CH:26]=4)[CH:31]=3)=[CH:36][CH:37]=2)=[CH:42][N:43]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 178451910HCID 178451910, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 57462071HCID 57462071, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of a TFA salt of (S)-tert-butyl 2-(5-(4-(6-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (50 mg) in DCM (10 mL) was added TFA (2.0 mL, 26 mmol) in one portion. The mixture was agitated at room temperature for 2 h. The reaction was concentrated under vacuum to yield a TFA salt of 2-((S)-pyrrolidin-2-yl)-5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazole (51.5 mg) as orange solid, which was used without further purification. LC-MS retention time 0.978 min; m/z 475.19 [M+H]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 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 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. HPLC-MS (TFA) 78457-087 using a Waters Sunfire C18 column 4 6×50 mm 5u showed the reaction was complete peak found at RT=0.978 min. MH+=475.19. 1H NMR (500 MHz, MeOD) δ ppm 8.34 (s, 1H), 8.20 (s, 1H), 8.03 (dd, J=14.2, 8.7 Hz, 2H), 7.84-7.96 (m, 7H), 7.79-7.84 (m, 1H), 4.99-5.11 (m, 2H), 3.48-3.63 (m, 4H), 2.57-2.70 (m, 2H), 2.41-2.55 (m, 2H), 2.29-2.41 (m, 2H), 2.15-2.29 (m, 2H).

Workup

  1. concentrationThe reaction was concentrated under vacuum

Sources & evidence

ORD record
ord-01acb4ac744b4b84b316a2b199d1eec7
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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