Acetic Acid → HCID 178474664, compound

HRID 1881418Notes

Reaction equation

HRID 1881418 reaction equation
[C:1]([OH:4])(=O)[CH3:2].[CH3:5][C:6]([CH3:30])([CH3:29])[CH2:7][C:8]1[N:9]=[C:10]([CH:13]([NH2:28])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][N:22]=3)=[CH:17][CH:16]=2)[NH:11][CH:12]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:5][C:6]([CH3:30])([CH3:29])[CH2:7][C:8]1[N:9]=[C:10]([CH:13]([NH:28][C:1](=[O:4])[CH3:2])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][N:22]=3)=[CH:17][CH:16]=2)[NH:11][CH:12]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178442242HCID 178442242, compound

Product 1

HCID 178474664HCID 178474664, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetic acid (24 μL, 0.43 mmol) was added to an ambient temperature solution of 1-[4-(2,2-dimethylpropyl)-1H-imidazol-2-yl]-2-[4-(5-fluoropyridin-2-yl)phenyl]ethanamine (for synthesis see Example 8) (76 mg, 0.22 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (83 mg, 0.43 mmol), 1-hydroxybenzotriazole (59 mg, 0.43 mmol) and sodium bicarbonate (183 mg, 2.2 mmol) in methylene chloride (3 mL). After stirring at ambient temperature overnight, the reaction mixture was quenched with brine and extracted with ethyl acetate. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Preparative plate chromatography eluting with 5% methanol/ethyl acetate afforded the title compound. High pressure liquid chromatography (Chiralcel AD column) eluting with 10% ethanol/hexane afforded the two pure enantiomers. 1H NMR (500 MHz, CD3OD) δ 8.48 (s, 1H), 7.87-7.80 (m, 3H), 7.68-7.62 (m, 2H), 7.24 (d, J=10 Hz, 2H), 6.66 (s, 1H), 5.22 (t, J=10 Hz, 1H), 3.35 (s, 3H), 3.29 (m, 1H), 3.18 (m, 1H), 2.40 (s, 2H) 0.86 (s, 9H); (M+H) found: 395.

Workup

  1. customthe reaction mixture was quenched with brine
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. concentrationconcentrated in vacuo
  5. washPreparative plate chromatography eluting with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-fec44a672306433998520c66b23d0b8c
Source dataset
uspto-grants-2012_11
Patent number
US08318767B2

Reaction notes

Loading…