Trifluoroacetic acid → HCID 70668495, compound

HRID 1471116Notes

Reaction equation

HRID 1471116 reaction equation
C(O)(C(F)(F)F)=O.C(OC(N1CCC[C@H]1C1NC2C=C(C3C=C4C(=CC=3)C=C(C3C=CC(C5NC([C@@H]6CCCN6C(OCC6C=CC=CC=6)=O)=NC=5)=CC=3)C=C4)C=CC=2N=1)=O)(C)(C)C.C(OC([N:72]1[CH2:76][CH2:75][CH2:74][C@H:73]1[C:77]1[NH:81][C:80]2[CH:82]=[C:83]([C:86]3[CH:95]=[C:94]4[C:89]([CH:90]=[CH:91][C:92]([C:96]5[CH:101]=[CH:100][C:99]([C:102]6[NH:106][C:105]([C@@H:107]7[CH2:111][CH2:110][CH2:109][N:108]7[C:112]([O:114][CH2:115][C:116]7[CH:121]=[CH:120][CH:119]=[CH:118][CH:117]=7)=[O:113])=[N:104][CH:103]=6)=[CH:98][CH:97]=5)=[CH:93]4)=[CH:88][CH:87]=3)[CH:84]=[CH:85][C:79]=2[N:78]=1)=O)(C)(C)C.N1CCC[C@H]1C1NC2C=C(C3C=C4C(=CC=3)C=C(C3C=CC(C5NC([C@@H]6CCCN6C(OCC6C=CC=CC=6)=O)=NC=5)=CC=3)C=C4)C=CC=2N=1>C(Cl)Cl>[NH:72]1[CH2:76][CH2:75][CH2:74][C@H:73]1[C:77]1[NH:81][C:80]2[CH:82]=[C:83]([C:86]3[CH:95]=[C:94]4[C:89]([CH:90]=[CH:91][C:92]([C:96]5[CH:97]=[CH:98][C:99]([C:102]6[NH:106][C:105]([C@@H:107]7[CH2:111][CH2:110][CH2:109][N:108]7[C:112]([O:114][CH2:115][C:116]7[CH:117]=[CH:118][CH:119]=[CH:120][CH:121]=7)=[O:113])=[N:104][CH:103]=6)=[CH:100][CH:101]=5)=[CH:93]4)=[CH:88][CH:87]=3)[CH:84]=[CH:85][C:79]=2[N:78]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid3×HCID 70666418HCID 70666418, compoundHCID 70666419HCID 70666419, compoundHCID 70668494HCID 70668494, compound

Product 1

HCID 70668495HCID 70668495, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of a TFA salt of (S)-benzyl 2-(5-(4-(6-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate and a TFA salt of (S)-benzyl 2-(5-(4-(7-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (381 mg) and TFA (2 mL) in CH2Cl2 (10 mL) was stirred at ambient conditions for 4 hours. The volatile component was removed in vacuo and the crude material was purified by a reverse phase HPLC (0 to 50% water/acetonitrile/NH4OAc) to provide a mixture of (S)-benzyl 2-(5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate and (S)-benzyl 2-(5-(4-(7-(2-((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (70 mg, 21% yield) as yellow oil. LC-MS retention time 2.87 min; Calcd. for C42H38N6O2 658.31 Found m/z 659.47 [M+H]+. 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 80% Solvent A/20% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min and an analysis time of 5 min where Solvent A was 5% acetonitrile/95% water/10 mmol NH4OAc and Solvent B was 95% acetonitrile/5% water/10 mmol NH4OAc. 1H NMR (Mixture of compounds, 500 MHz, MeOD) δ ppm 8.07-8.24 (m, 4H), 7.91-8.03 (m, 6H), 7.73-7.89 (m, 12H), 7.66-7.73 (m, 4H), 7.27-7.46 (m, 6H), 7.09-7.18 (m, 4H), 6.97-7.04 (m, 2H), 5.01-5.21 (m, 5H), 4.83-5.01 (m, 2H), 3.72-3.82 (m, 2H), 3.53-3.65 (m, 2H), 3.42-3.52 (m, 2H), 3.35-3.42 (m, 4H), 2.48-2.62 (m, 2H), 2.28-2.47 (m, 4H), 2.04-2.24 (m, 8H).

Workup

  1. customThe volatile component was removed in vacuo
  2. customthe crude material was purified by a reverse phase HPLC (0 to 50% water/acetonitrile/NH4OAc)
  3. customto provide

Sources & evidence

ORD record
ord-54a039d0ac624b5782d859554cea9610
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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