Triethylamine → HCID 178489993, compound

HRID 1627266Notes

Reaction equation

HRID 1627266 reaction equation
[NH2:1][C@@H:2]([CH2:6][CH2:7][CH2:8][NH:9][C:10](=[O:45])[C:11]1[CH:16]=[C:15]([F:17])[C:14]([CH2:18][S:19][C:20]2[N:21]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[C:22]([C:25]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][CH3:36])[CH:29]=3)([CH3:27])[CH3:26])=[CH:23][N:24]=2)=[C:13]([Cl:44])[CH:12]=1)[C:3]([OH:5])=[O:4].C([NH:53][C:54](N1C=CC=N1)=[N:55]C(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C>CO>[Cl:44][C:13]1[CH:12]=[C:11]([CH:16]=[C:15]([F:17])[C:14]=1[CH2:18][S:19][C:20]1[N:21]([C:37]2[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=2)[C:22]([C:25]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][CH3:36])[CH:29]=2)([CH3:27])[CH3:26])=[CH:23][N:24]=1)[C:10]([NH:9][CH2:8][CH2:7][CH2:6][C@H:2]([NH:1][C:54]([NH2:55])=[NH:53])[C:3]([OH:5])=[O:4])=[O:45]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 4428040N,N'-Bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidineHCID 66740048HCID 66740048, compound

Product 1

HCID 178489993HCID 178489993, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (S)-2-amino-5-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)pentanoic acid (268 mg, 0.40 mmol), N,N′-di-Boc-1H-pyrazole-1-carboxamidine (135 mg, 0.44 mmol) and triethylamine (175 μL, 1.19 mmol) in MeOH (10 mL) was stirred at 25° C. for 18 h. The reaction mixture was concentrated and reconstituted in EtOAc. The organic layer was washed with 1N HCl (3×5 mL), sat. aq. NaHCO3 (5 mL), dried over Na2SO4 and concentrated to a colorless oil. To the oil was added 4N HCl in Dioxane (10 mL) at 25° C. and stirred for 18 h. Upon completion, the reaction mixture was concentrated and purified by flash chromatography (MeOH/DCM, 0-20%) to give the title product (64 mg, 28% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.91 (t, J=5.2 Hz, 1H), 7.76 (s, 1H), 7.61 (dd, J=10.1, 1.0 Hz, 1H), 7.50-7.10 (br s, 4H), 7.45 (d, J=6.6 Hz, 2H), 7.21 (d, J=8.3 Hz, 1H), 7.17 (s, 1H), 6.95 (t, J=8.4 Hz, 2H), 6.58-6.43 (m, 4H), 4.06 (s, 2H), 3.77 (d, J=4.6 Hz, 1H), 3.67 (s, 3H), 3.23 (s, 2H), 1.71-1.59 (m, 2H), 1.58-1.46 (m, 2H), 1.46 (s, 6H). MS (EI) m/z 719 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washThe organic layer was washed with 1N HCl (3×5 mL), sat. aq. NaHCO3 (5 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a colorless oil
  5. additionTo the oil was added 4N HCl in Dioxane (10 mL) at 25° C.
  6. concentrationUpon completion, the reaction mixture was concentrated
  7. custompurified by flash chromatography (MeOH/DCM, 0-20%)

Sources & evidence

ORD record
ord-446fdcec72364210a6917b64460e627b
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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