Triethylamine → 7-(4-Fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxamide

HRID 592332Notes

Reaction equation

HRID 592332 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]3[NH:14][C:15](=[O:22])[N:16]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[C:12]=3[CH:11]=[C:10]([C:23](O)=[O:24])[CH:9]=2)=[CH:4][CH:3]=1.Cl.[CH3:27][C:28]1[N:32]=[C:31]([C@H:33]([NH2:35])[CH3:34])[O:30][N:29]=1.ON1C2N=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]3[NH:14][C:15](=[O:22])[N:16]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[C:12]=3[CH:11]=[C:10]([C:23]([NH:35][C@@H:33]([C:31]3[O:30][N:29]=[C:28]([CH3:27])[N:32]=3)[CH3:34])=[O:24])[CH:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 66661266(R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethanamine hydrochlorideHCID 666901397-(4-Fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylic acid

Product 1

HCID 469167007-(4-Fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxamideYield 39.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 7-(4-fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylic acid (40 mg, 0.069 mmol), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine hydrochloride (13.6 mg, 0.083 mmol), 1-hydroxy-7-azabenzotriazol (1.88 mg, 0.014 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (23.2 mg, 0.121 mmol) was added N,N-dimethylformamide (0.138 mL) followed by triethylamine (0.048 mL, 0.346 mmol). Reaction heated at 50° C. for 1.5 h. Reaction cooled and filtered. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% TPA) gave the title compound (12.5 mg): LC-MS [M+1]=454.4; HRMS [M+1] found=454.1884; 1H NMR (500 MHz, CHCl3-d): δ 7.65 (1H, s), 7.51-7.47 (3H, m), 7.22-7.15 (2H, m), 6.97 (1H, d, J=7.81 Hz), 5.60-5.52 (1H, m), 3.85 (2H, s), 3.12 (1H, s), 2.35 (3H, s), 1.69 (3H, d, J=7.10 Hz), 1.29 (6H, s).

Workup

  1. customReaction
  2. customReaction
  3. temperaturecooled
  4. filtrationfiltered
  5. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% TPA)

Sources & evidence

ORD record
ord-f6fd308a7b894d798b2b4edd154fb7bc
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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