Diisopropylethylamine → ethyl(4-{(S)-{[(4-tert-butylphenyl)acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)acetate

HRID 877383

Reaction equation

HRID 877383 reaction equation
[Cl-].[Cl-].[NH3+:3][C@@H:4]([C:17]1[N:18]=[N:19][N:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:21]=1)[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[CH:7][NH+:6]=1.[C:28]([C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39](O)=[O:40])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O.C(Cl)Cl>[CH2:26]([O:25][C:23](=[O:24])[CH2:22][N:20]1[CH:21]=[C:17]([C@H:4]([NH:3][C:39](=[O:40])[CH2:38][C:35]2[CH:36]=[CH:37][C:32]([C:28]([CH3:30])([CH3:29])[CH3:31])=[CH:33][CH:34]=2)[C:5]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]([F:16])([F:14])[F:15])=[CH:7][N:6]=2)[N:18]=[N:19]1)[CH3:27]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 118343Benzeneacetic acid, 4-(1,1-dimethylethyl)-HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866689672-{(S)-ammonio[1-(2-ethoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl]methyl}-5-(2,2,2-trifluoroethoxy)pyridinium dichloride

Product 1

HCID 131732598ethyl(4-{(S)-{[(4-tert-butylphenyl)acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)acetateYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 100 ml round bottom flask equipped with a magnetic stir bar were added 2-{(S)-ammonio[1-(2-ethoxy-2-oxoethyl)-1H-1,2,3-triazol-4-yl]methyl}-5-(2,2,2-trifluoroethoxy)pyridinium dichloride (0.265 g, 0.614 mmol), 4-tert-butylphenylacetic acid (0.118 g, 0.614 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.118 g, 0.614 mmol), 1-hydroxy-7-azabenzotriazole (0.084 g, 0.614 mmol) and diisopropylethylamine (0.236 ml, 1.350 mmol) into 10.0 ml of CH2Cl2. The resulting solution was stirred at room temperature for 2 hours. The reaction mixture was diluted with water and the two layers were separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 0.150 g (46%) of the title compound. 1H NMR (CDCl3, 400 MHz) δ 8.219 (s, 1H), 7.610 (m, 2H), 7.340 (m, 3H), 7.255 (m, 1H), 7.184 (m, 2H), 6.322 (d, J=7.96 Hz, 1H), 5.041 (s, 2H), 4.347 (q, J=7.97 Hz, 2H), 4.210 (q, J=7.14 Hz, 2H), 3.912 (br s, 1H), 3.585 (s, 2H), 1.278 (s, 9H), 1.249 (t, J=7.19 Hz, 3H). ES-MS [M+1]+: 534.3.

Workup

  1. customTo a 100 ml round bottom flask equipped with a magnetic stir bar
  2. customthe two layers were separated
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuum
  8. customPurification
  9. additionby preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column)

Sources & evidence

ORD record
ord-988e9b41e6fb41f189df7bc2db3e8035
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Linked notes

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