Trifluoroacetic acid → HCID 178419811, compound

HRID 1471137Notes

Reaction equation

HRID 1471137 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]1[NH:21][C:22]([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[CH:31]=[C:30]([C:35]2[CH:36]=[C:37]4[C:57](=[CH:58][CH:59]=2)[C:41]2[NH:42][C:43]([C@@H:45]5[CH2:49][CH2:48][CH2:47][N:46]5C(OC(C)(C)C)=O)=[N:44][C:40]=2[CH:39]=[CH:38]4)[CH:29]=[CH:28]3)=[CH:23][N:24]=1)=O)(C)(C)C>C(Cl)Cl>[NH:46]1[CH2:47][CH2:48][CH2:49][C@H:45]1[C:43]1[NH:42][C:41]2[C:57]3[C:37]([CH:38]=[CH:39][C:40]=2[N:44]=1)=[CH:36][C:35]([C:30]1[CH:29]=[CH:28][C:27]2[C:32](=[CH:33][CH:34]=[C:25]([C:22]4[NH:21][C:20]([C@@H:16]5[CH2:17][CH2:18][CH2:19][NH:15]5)=[N:24][CH:23]=4)[CH:26]=2)[CH:31]=1)=[CH:59][CH:58]=3

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451931HCID 178451931, compound

Product 1

HCID 178419811HCID 178419811, compoundYield 102%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 26.0 mmol) was added in one portion to a stirred solution of (5)-tert-butyl 2-(7-(6-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (137 mg) in CH2Cl2 (10 mL) at room temperature. The mixture was stirred for 2 h at room temp. and then the solvents were removed in vacuo. The residue was taken up in 50% methanol/CH2Cl2 and filtered through an MCX cartridge (Strata XC). The cartridge was washed with methanol and the compound was eluted with a solution of NH3 in methanol (2M). The appropriate fractions were concentrated in vacuo to afford 2-((S)-pyrrolidin-2-yl)-7-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)-1H-naphtho[1,2-d]imidazole (98 mg, 0.20 mmol) as orange solid. LC-MS retention time 1.245 min; m/z 499.30 (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 (TFA salt, 500 MHz, MeOD) δ ppm 8.59 (d, J=8.5 Hz, 1H), 8.43 (d, J=1.5 Hz, 1H), 8.36 (s, 1H), 8.31 (s, 1H), 8.13 (dd, J=8.6, 1.8 Hz, 1H), 8.01-8.10 (m, 3H), 7.90-7.98 (m, 2H), 7.87 (s, 1H), 7.80 (d, J=8.6 Hz, 1H), 5.18 (t, J=7.9 Hz, 1H), 5.05 (t, J=8.1 Hz, 1H), 3.63-3.72 (m, 1H), 3.52-3.63 (m, 3H), 2.61-2.77 (m, 2H), 2.45-2.58 (m, 2H), 2.33-2.43 (m, 2H), 2.20-2.33 (m, 2H).

Workup

  1. customthe solvents were removed in vacuo
  2. filtrationfiltered through an MCX cartridge (Strata XC)
  3. washThe cartridge was washed with methanol
  4. washthe compound was eluted with a solution of NH3 in methanol (2M)
  5. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-cbe24a4bcbc942709192f637945a393f
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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