Trifluoroacetic acid → HCID 178502291, compound

HRID 535135Notes

Reaction equation

HRID 535135 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[CH:16]([C:17]2[NH:18][CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35]=[C:36]([C@@H:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:54])[C@H:45]([CH:51]([CH3:53])[CH3:52])[NH:46][C:47]([O:49][CH3:50])=[O:48])[NH:37][CH:38]=5)=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[N:21]=2)[CH2:15][C:14]2([CH2:59][CH2:58][N:57](C(OC(C)(C)C)=O)[CH2:56][CH2:55]2)[CH2:13]1)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:52][CH:51]([CH3:53])[C@H:45]([NH:46][C:47](=[O:48])[O:49][CH3:50])[C:44]([N:40]1[CH2:41][CH2:42][CH2:43][C@H:39]1[C:36]1[NH:37][CH:38]=[C:34]([C:31]2[CH:32]=[CH:33][C:28]([C:25]3[CH:24]=[CH:23][C:22]([C:20]4[N:21]=[C:17]([CH:16]5[CH2:15][C:14]6([CH2:55][CH2:56][NH:57][CH2:58][CH2:59]6)[CH2:13][N:12]5[C:10](=[O:11])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:7]([CH3:8])[CH3:9])[NH:18][CH:19]=4)=[CH:27][CH:26]=3)=[CH:29][CH:30]=2)[N:35]=1)=[O:54]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178502294tert-butyl 3-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-2-[5-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-3,8-diazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 178502291HCID 178502291, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-3-(4-{4′-[2-((2S)-1-{N-[(methyloxy)carbonyl]-L-valyl}-2-pyrrolidinyl)-1H-imidazol-4-yl]-4-biphenylyl}-1H-imidazol-2-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate (68 mg, 0.08 mmol) in anhydrous CH2Cl2 (1 mL) was added trifluoroacetic acid (0.3 mL) and the reaction stirred at room temperature for 2 h. The reaction was concentrated in vacuo and purified by HPLC eluting with 10-90% acetonitrile/water/0.2% NH4OH to afford the title compound as a tan solid (49 mg, 81% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.56-7.83 (m, 10H) 7.31 (br. s., 2H) 5.00-5.22 (m, 2H) 4.12-4.30 (m, 3H) 4.01 (br. s., 1H) 3.80-3.91 (m, 1H) 3.57-3.70 (m, 6H) 2.76-3.07 (m, 4H) 1.89-2.48 (m, 10H) 1.69-1.81 (m, 1H) 1.61 (br. s., 2H) 0.82-1.09 (m, 15H). HRMS for C44H58N9O6 (M+H)+ calc: 808.4510. found: 808.4509. Purity (LC-MS): 94%.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompurified by HPLC
  3. washeluting with 10-90% acetonitrile/water/0.2% NH4OH

Sources & evidence

ORD record
ord-be4016ba4fdb4186866e3dc5e020f0ea
Source dataset
uspto-grants-2014_10
Patent number
US08853416B2

Reaction notes

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