Triethylamine → HCID 178490003, compound

HRID 1627280Notes

Reaction equation

HRID 1627280 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][S:6]([C:9]1[CH:14]=[C:13]([F:15])[C:12]([CH2:16][S:17][C:18]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:20]([C:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([O:33][CH3:34])[CH:27]=3)([CH3:25])[CH3:24])=[CH:21][N:22]=2)=[C:11]([F:42])[CH:10]=1)(=[O:8])=[O:7].C([NH:50][C:51](N1C=CC=N1)=[N:52]C(OC(C)(C)C)=O)(OC(C)(C)C)=O.CCN(CC)CC>CO>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]([C:20]2[N:19]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:18]([S:17][CH2:16][C:12]3[C:11]([F:42])=[CH:10][C:9]([S:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][C:51]([NH2:52])=[NH:50])(=[O:7])=[O:8])=[CH:14][C:13]=3[F:15])=[N:22][CH:21]=2)([CH3:25])[CH3:24])=[CH:27][C:28]=1[O:33][CH3:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 4428040N,N'-Bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidineHCID 66740710HCID 66740710, compound

Product 1

HCID 178490003HCID 178490003, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of N-(3-aminopropyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzenesulfonamide (172 mg, 0.27 mmol), N,N′-di-Boc-1H-pyrazole-1-carboxamidine (100 mg, 0.32 mmol) and Et3N (190 μL, 1.35 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), satd 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 preparatory HPLC (MeCN/H2O with 0.1% TFA, 10-99%) to give the title product (54 mg, 28% yield) as white solid. 1H NMR (400 MHz, MeOD) δ 7.99 (s, 1H), 7.51 (s, 2H), 7.37 (s, 1H), 7.28 (d, J=5.7 Hz, 1H), 6.98 (s, 2H), 6.62 (s, 2H), 6.56 (s, 2H), 4.14 (s, 2H), 3.73 (s, 3H), 3.70-3.54 (m, 3H), 3.30-3.21 (m, 2H), 3.00 (s, 2H), 1.80 (s, 2H), 1.63 (s, 6H); MS (EI) m/z 681 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washThe organic layer was washed with 1N HCl (3×5 mL), satd 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 preparatory HPLC (MeCN/H2O with 0.1% TFA, 10-99%)

Sources & evidence

ORD record
ord-119d14ac653a4718861c5a1cabdffa77
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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