Triethylamine → 4-(4-Fluorophenyl)-2-(2-hydroxy-2-methylpropyl)-1-methyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazole-5-yl)ethyl]-1H-benzimidazole-6-carboxamide

HRID 592325Notes

Reaction equation

HRID 592325 reaction equation
C[C:2]1[C:16]([C:17](O)=[O:18])=[CH:15][C:5]2[N:6]([CH3:14])[C:7]([CH2:9][C:10]([OH:13])([CH3:12])[CH3:11])=[N:8][C:4]=2[C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1.Cl.[CH3:28][C:29]1[N:33]=[C:32]([C@H:34]([NH2:36])[CH3:35])[O:31][N:30]=1.ON1C2N=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C=O)C>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:3]2[C:4]3[N:8]=[C:7]([CH2:9][C:10]([OH:13])([CH3:11])[CH3:12])[N:6]([CH3:14])[C:5]=3[CH:15]=[C:16]([C:17]([NH:36][C@@H:34]([C:32]3[O:31][N:30]=[C:29]([CH3:28])[N:33]=3)[CH3:35])=[O:18])[CH:2]=2)=[CH:25][CH:24]=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 66689965Methyl 4-(4-fluorophenyl)-2-(2-hydroxy-2-methylpropyl)-1-methyl-1H-benzimidazole-6-carboxylic acid

Product 1

HCID 469166554-(4-Fluorophenyl)-2-(2-hydroxy-2-methylpropyl)-1-methyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazole-5-yl)ethyl]-1H-benzimidazole-6-carboxamideYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of methyl 4-(4-fluorophenyl)-2-(2-hydroxy-2-methylpropyl)-1-methyl-1H-benzimidazole-6-carboxylic acid (122 mg, 0.236 mmol), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine hydrochloride (46.3 mg, 0.283 mmol), 1-hydroxy-7-azabenzotriazol (3.21 mg, 0.024 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (79 mg, 0.412 mmol) was added DMF (0.471 mL) followed by triethylamine (0.099 mL, 0.707 mmol). Reaction heated at 50° C. for 30 min. Reaction cooled and filtered. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% TFA) gave the title compound (87.4 mg): LC-MS [M+1]=452.4; 1H NMR (500 MHz, CHCl3-d): δ 7.94 (2H, m), 7.90 (1H, s), 7.77 (1H, s), 7.20 (1H, d, J=7.73 Hz), 7.15 (2H, t, J=8.51 Hz), 5.66-5.59 (1H, m), 5.47 (1H, s), 3.78 (3H, s), 3.02 (2H, s), 2.39 (3H, s), 1.74 (5H, d, J=7.14 Hz), 1.35 (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% TFA)

Sources & evidence

ORD record
ord-2a4a4903cdd143fa9f822d7d8e7e3ddc
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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