Triethylamine → Methyl 7-(4-fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylate

HRID 592330Notes

Reaction equation

HRID 592330 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:15]([O:17][CH3:18])=[O:16])=[CH:4][C:3]=1[NH:19][CH2:20][C:21]([OH:24])([CH3:23])[CH3:22].C(N(CC)CC)C.Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl.C(=O)(O)[O-].[Na+]>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]3[NH:1][C:33](=[O:35])[N:19]([CH2:20][C:21]([OH:24])([CH3:22])[CH3:23])[C:3]=3[CH:4]=[C:5]([C:15]([O:17][CH3:18])=[O:16])[CH:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 66693327Methy 6-amino-4'-fluoro-5-[(2-hydroxy-2-methylpropyl)amino]biphenyl-3-carboxylate

Product 1

HCID 66690107Methyl 7-(4-fluorophenyl)-3-(2-hydroxy-2-methylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylateYield 83.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of methy 6-amino-4′-fluoro-5-[(2-hydroxy-2-methylpropyl)amino]biphenyl-3-carboxylate (180 mg, 0.542 mmol) in dichloromethane (16.2 mL) was added triethylamine (0.091 mL, 0.650 mmol) followed by triphosgene (80.0 mg, 0.271 mmol) in dichloromethane (5.42 mL). Reaction heated at 30° C. for 4 h. Reaction was cooled, diluted with saturated sodium bicarbonate and dichloromethane. Adjusted aqueous layer to pH=14. Wash aqueous with dichloromethane (5×). Combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% NOH) gave the title compound (81.0 mg): LC-MS [M+1]=359.2.

Workup

  1. customReaction
  2. customReaction
  3. temperaturewas cooled
  4. dry with materialCombined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% NOH)

Sources & evidence

ORD record
ord-51326e9465ae4a59940cc7c37c580db5
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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