Trifluoroacetic acid → HCID 178478350, compound

HRID 1471142Notes

Reaction equation

HRID 1471142 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[C@H:20]([C:21]2[NH:25][C:24]3[CH:26]=[CH:27][C:28]([C:30]4[CH:31]=[C:32]5[C:37](=[CH:38][CH:39]=4)[CH:36]=[C:35]([C:40]4[N:41]=[C:42]([C@@H:46]6[CH2:51][C@@H:50]7[C@@H:48]([CH2:49]7)[N:47]6C(OC(C)(C)C)=O)[NH:43][C:44]=4[Cl:45])[CH:34]=[CH:33]5)=[CH:29][C:23]=3[N:22]=2)[CH2:19][C@@H:18]2[C@H:16]1[CH2:17]2)=O)(C)(C)C>C(Cl)Cl>[C@@H:16]12[CH2:17][C@@H:18]1[CH2:19][C@@H:20]([C:21]1[NH:25][C:24]3[CH:26]=[CH:27][C:28]([C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[C:35]([C:40]6[NH:41][C:42]([C@@H:46]7[CH2:51][C@@H:50]8[C@@H:48]([CH2:49]8)[NH:47]7)=[N:43][C:44]=6[Cl:45])[CH:36]=5)[CH:31]=4)=[CH:29][C:23]=3[N:22]=1)[NH:15]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 178452521HCID 178452521, compound

Product 1

HCID 178478350HCID 178478350, compoundYield 78.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 26.0 mmol) was added to a solution of a TFA salt of tert-butyl (1R,3S,5R)-3-(4-(6-(2-((1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-benzimidazol-5-yl)-2-naphthyl)-5-chloro-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (131 mg, 0.140 mmol) in DCM (10 mL) and the mixture was stirred for 3 h at rt. The volatiles were removed under vacuum and the residue was taken into MeOH and filtered through a Strata XC MCX cartridge. The cartridge was washed with methanol and the compound was release from the cartridge by eluting with a solution of 2M of ammonia/methanol. The ammonia/methanol filtrate was evaporated under reduced pressure to yield 2-((1R,3S,5R)-2-azabicyclo[3.1.0]hex-3-yl)-5-(6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hex-3-yl)-4-chloro-1H-imidazol-5-yl)-2-naphthyl)-1H-benzimidazole (55 mg, 0.11 mmol) as tan solid. LC-MS retention time 1.375 min; m/z 507.33 (1:1) (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire C18 4.6×30 mm 5 μm 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% methanol/90% water/0.1% TFA and Solvent B was 10% water/90% methanol/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 8.26 (s, 1H), 8.19 (s, 1H), 8.00-8.09 (m, 3H), 7.92 (ddd, J=12.1, 8.6, 1.8 Hz, 2H), 7.85 (dd, J=8.6, 1.5 Hz, 1H), 7.81 (d, J=8.6 Hz, 1H), 4.96 (dd, J=11.0, 7.6 Hz, 1H), 4.64 (app t, J=9.3 Hz, 1H), 3.53-3.59 (m, 1H), 3.44-3.50 (m, 1H), 2.82 (dd, J=13.0, 7.5 Hz, 1H), 2.61-2.74 (m, 3H), 2.03-2.15 (m, 2H), 1.24-1.30 (m, 1H), 1.18-1.24 (m, 1H), 0.96-1.09 (m, 2H).

Workup

  1. customThe volatiles were removed under vacuum
  2. filtrationfiltered through a Strata XC MCX cartridge
  3. washThe cartridge was washed with methanol
  4. washby eluting with a solution of 2M of ammonia/methanol
  5. customThe ammonia/methanol filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-84f147e7676042a783604fd027b688b5
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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