Dichloromethane → HCID 178461189, compound

HRID 1471163Notes

Reaction equation

HRID 1471163 reaction equation
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C(OC([N:15]1[C@@H:19]([CH3:20])[CH2:18][CH2:17][C@H:16]1[C:21]1[NH:22][CH:23]=[C:24]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[CH:32]=[C:31]([C:36]2[CH:41]=[CH:40][C:39]([C:42]4[N:43]=[C:44]([C@@H:47]5[CH2:51][CH2:50][C@H:49]([CH3:52])[N:48]5C(OC(C)(C)C)=O)[NH:45][CH:46]=4)=[CH:38][CH:37]=2)[CH:30]=[CH:29]3)[N:25]=1)=O)(C)(C)C.C(Cl)Cl>ClCCCl>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[CH3:52][C@@H:49]1[NH:48][C@H:47]([C:44]2[NH:45][CH:46]=[C:42]([C:39]3[CH:40]=[CH:41][C:36]([C:31]4[CH:30]=[CH:29][C:28]5[C:33](=[CH:34][CH:35]=[C:26]([C:24]6[N:25]=[C:21]([C@@H:16]7[CH2:17][CH2:18][C@H:19]([CH3:20])[NH:15]7)[NH:22][CH:23]=6)[CH:27]=5)[CH:32]=4)=[CH:37][CH:38]=3)[N:43]=2)[CH2:51][CH2:50]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acid3×HCID 178461188tert-butyl (2S,5S)-2-(4-(4-(6-(2-((2S,5S)-1-(tert-butoxycarbonyl)-5-methyl-2-pyrrolidinyl)-1H-imidazol-4-yl)-2-naphthyl)phenyl)-1H-imidazol-2-yl)-5-methyl-1-pyrrolidinecarboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 178461189HCID 178461189, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

TFA (0.500 mL, 6.49 mmol) was added dropwise to a stirred solution of tert-butyl (2S,5S)-2-(4-(4-(6-(2-((2S,5S)-1-(tert-butoxycarbonyl)-5-methyl-2-pyrrolidinyl)-1H-imidazol-4-yl)-2-naphthyl)phenyl)-1H-imidazol-2-yl)-5-methyl-1-pyrrolidinecarboxylate (228 mg, 0.324 mmol) in DCE (6 mL). During the addition, precipitate formed which hindered the stirring. DCM (˜10 mL) was added and the slurry was stirred while the remaining TFA was added. The reaction was stirred at rt for 30 min, additional TFA was added (˜0.5 mL) and the reaction was stirred 3 h. The reaction was concentrated to yield a TFA salt of 2-((2S,5S)-5-methyl-2-pyrrolidinyl)-4-(4-(6-(2-((2S,5S)-5-methyl-2-pyrrolidinyl)-1H-imidazol-4-yl)-2-naphthyl)phenyl)-1H-imidazole (102 mg, 113 mg, 114 mg) as an orange solid. LC-MS retention time 2.756 min; m/z 503.14 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u C18 3.0×50 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 5% MeOH/95% H2O/10 mM ammonium acetate and Solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) δ ppm 8.32 (s, 1 H), 8.17 (s, 1 H), 8.01 (app t, J=8.2 Hz, 2 H), 7.85-7.95 (m, 6 H), 7.80 (s, 1 H), 7.73 (s, 1 H), 5.02 (app q, J=8.0 Hz, 2 H), 3.92 (dddd, J=8.7, 7.0, 6.9, 4.8 Hz, 2 H), 2.52-2.67 (m, 4 H), 2.38-2.49 (m, 2 H), 1.95-2.07 (m, 2 H), 1.55 (app dd, J=6.7, 4.4 Hz, 6 H).

Workup

  1. additionDuring the addition, precipitate
  2. customformed which
  3. additionwas added
  4. stirringthe reaction was stirred 3 h
  5. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-352af0ec1873475fbc1b73d816849be0
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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