Trifluoroacetic acid → HCID 178478349, compound

HRID 625586Notes

Reaction equation

HRID 625586 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: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][C:42]=4[Cl:58])=[CH:37][CH:36]=2)[CH:29]=[CH:28]3)=[CH:23][N:24]=1)=O)(C)(C)C>C(Cl)Cl>[Cl:58][C:42]1[N:43]=[C:44]([C@@H:46]2[CH2:50][CH2:49][CH2:48][NH:47]2)[NH:45][C:41]=1[C:38]1[CH:37]=[CH:36][C:35]([C:30]2[CH:29]=[CH:28][C:27]3[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]=3)[CH:31]=2)=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451932HCID 178451932, compound

Product 1

HCID 178478349HCID 178478349, compoundYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL) was added to a solution of (S)-tert-butyl 2-(5-(4-(6-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-4-chloro-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (75 mg) in DCM (10 mL) and the mixture was stirred for 2 h at room temperature. The solvents were removed in vacuo and the residue was taken up in a solvent mixture of 1:1 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 4-chloro-2-((S)-pyrrolidin-2-yl)-5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazole (40 mg, 0.079 mmol) as yellow solid. LC-MS retention time 1.353 min; m/z 509.32 (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, partially soluble only) δ ppm 8.20 (s, 1H), 8.09 (s, 1H), 7.88-7.96 (m, 2H), 7.76-7.88 (m, 6H), 7.51 (s, 1H), 4.50 (t, J=7.28 Hz, 1H), 4.35 (t, J=7.15 Hz, 1H), 3.03-3.31 (partially masked by methanol, m, 4H), 2.24-2.42 (m, 2H), 1.88-2.21 (m, 6H).

Workup

  1. customThe solvents were removed in vacuo
  2. additionthe residue was taken up in a solvent mixture of 1:1 methanol/CH2Cl2
  3. filtrationfiltered through an MCX cartridge (Strata XC)
  4. washThe cartridge was washed with methanol
  5. washthe compound was eluted with a solution of NH3 in methanol (2M)
  6. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-f105d0d31bcf46c595a8d229422eea78
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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