Hydrochloric Acid → Hydrochloric Acid
Reaction equation
[ClH:1].O1CCOCC1.C(O)(C(F)(F)F)=O.[CH3:15][O:16][C:17]([NH:19][C@@H:20]([CH:68]([CH3:70])[CH3:69])[C:21]([N:23]1[C@H:28]([C:29]2[NH:30][C:31]([C:34]3[CH:39]=[CH:38][C:37]([C:40]4[CH:41]=[C:42]5[C:47](=[CH:48][CH:49]=4)[CH:46]=[C:45]([C:50]4[NH:54][C:53]([C@@H:55]6[CH2:60][C@@H:59]7[C@@H:57]([CH2:58]7)[N:56]6C(OC(C)(C)C)=O)=[N:52][CH:51]=4)[CH:44]=[CH:43]5)=[CH:36][CH:35]=3)=[CH:32][N:33]=2)[CH2:27][C@@H:26]2[C@H:24]1[CH2:25]2)=[O:22])=[O:18]>C(Cl)Cl>[ClH:1].[ClH:1].[C@@H:57]12[CH2:58][C@@H:59]1[CH2:60][C@@H:55]([C:53]1[NH:54][C:50]([C:45]3[CH:46]=[C:47]4[C:42](=[CH:43][CH:44]=3)[CH:41]=[C:40]([C:37]3[CH:38]=[CH:39][C:34]([C:31]5[NH:30][C:29]([C@@H:28]6[CH2:27][C@@H:26]7[C@@H:24]([CH2:25]7)[N:23]6[C:21](=[O:22])[C@@H:20]([NH:19][C:17](=[O:18])[O:16][CH3:15])[CH:68]([CH3:70])[CH3:69])=[N:33][CH:32]=5)=[CH:35][CH:36]=3)[CH:49]=[CH:48]4)=[CH:51][N:52]=1)[NH:56]2Participants
Reactant 4
HCID 313Hydrochloric Acid
HCID 6422Trifluoroacetic acid
HCID 312751,4-Dioxane
HCID 58498832(1R,3S,5R)-tert-butyl 3-(5-(6-(4-(2-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylateProduct 2
Reagents, catalysts & solvents 1
Procedure
4N HCl in dioxane (2 mL, 8.00 mmol) was added to a stirred solution of a TFA salt of (1R,3S,5R)-tert-butyl 3-(5-(6-(4-(2-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)phenyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (0.10 g, 0.12 mmol) in CH2Cl2 (20 mL) and the resulting yellow suspension was stirred at rt for 2 h. The reaction was concentrated under vacuum and the resulting residue was triturated with Et2O to yield an HCl salt of methyl(S)-1-((1R,3S,5R)-3-(5-(4-(6-(2-((1R,3S,5R)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate HCl (47 mg) as a yellow solid. LC/MS [M+H]+=656; Rt=1.73 min is product. Column Luna 3u C18 2×50 mm; start % B: 0, final % B: 100 Solvent A: 10% Acetonitrile/90% H2O+1% TFA; Solvent B: 90% Acetonitrile/10% H2O+1% TFA; flow rate 4 ml/min. Run time: 5 min. Purity=95%. 1H NMR (500 MHz, DMSO-d6) δ ppm 14.47-15.18 (2 H, m), 9.77-10.61 (2 H, m), 8.30-8.42 (2 H, m), 8.17 (1 H, s), 7.93-8.10 (10 H, m), 7.27 (1 H, d, J=8.55 Hz), 5.08 (1 H, t, J=7.93 Hz), 4.71 (1 H, t, J=8.39 Hz), 4.40-4.46 (1 H, m), 3.77 (1 H, br. s.), 3.52-3.58 (3 H, m), 3.38-3.44 (1 H, m), 2.52-2.61 (3 H, m), 2.39 (1 H, dt, J=13.58, 6.64 Hz), 2.14-2.21 (1 H, m), 1.94 (2 H, dd, J=8.24, 4.88 Hz), 1.15 (1 H, d, J=5.80 Hz), 0.93 (4 H, d, J=6.71 Hz), 0.75-0.89 (6 H, m).
Workup
- concentrationThe reaction was concentrated under vacuum
- customthe resulting residue was triturated with Et2O
Sources & evidence
- ORD record
- ord-c7bfa7d48e4d4629afdccf791e824c75
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09006455B2
Reaction notes
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