Ammonium formate → HCID 178457838, compound

HRID 518743Notes

Reaction equation

HRID 518743 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:21]([O-])=O)=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@H:12]([C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:7]=1.C([O-])=O.[NH4+]>CCO.[Pd]>[NH2:21][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][C:6]=1[NH:8][C@@H:9]1[CH2:10][CH2:11][C@H:12]([C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 178457839HCID 178457839, compound

Product 1

HCID 178457838HCID 178457838, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of cis-4-(5-fluoro-2-nitrophenylamino)-N-isopropylcyclohexanecarboxamide (123 mg, 0.380 mmol) in EtOH (5 mL) was added ammonium formate (240 mg, 3.80 mmol) and 10% palladium on carbon (40.5 mg, 0.038 mmol). The reaction was stirred at RT for 1 hour. The reaction mixture was filtered through Celite® brand filter aid (washed with MeOH), concentrated, and redissolved in DCM (10 mL). The solution was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to afford cis-4-(2-amino-5-fluorophenylamino)-N-isopropylcyclohexanecarboxamide as a purple oil that crystallized upon standing. The diamine was dissolved in THF (5 mL), cooled to 0° C., and 4-fluorobenzoyl isothiocyanate (97 mg, 0.534 mmol) was added. The reaction was stirred at 0° C. for 15 minutes, and then DIPEA (0.100 mL, 0.573 mmol) and EDC (110 mg, 0.573 mmol) were added, and the reaction was stirred for 1 hour at 60° C. The reaction mixture was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(6-fluoro-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as an off-white powder (137 mg, 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (d, J=6.7 Hz, 6H), 1.55-1.80 (m, 4H), 2.04-2.12 (m, 2H), 2.53 (br. s., 1H), 2.68-2.82 (m, 2H), 3.94-4.08 (m, 1H), 4.86 (br. s., 1H), 7.02-7.12 (m, 1H), 7.25 (dd, J=8.9 Hz, 8.9 Hz, 2H), 7.53 (dd, J=8.8, 4.9 Hz, 1H), 7.60 (dd, J=9.5, 1.9 Hz, 1H), 7.70 (d, J=7.4 Hz, 1H), 8.32 (dd, J=8.8, 5.9 Hz, 2H), 12.82 (s, 1H). MS, m/z (C24H26F2N4O2): calcd, 440.2. found, 440.7 [M+H].

Workup

  1. filtrationThe reaction mixture was filtered through Celite® brand
  2. filtrationfilter
  3. washaid (washed with MeOH)
  4. concentrationconcentrated
  5. dissolutionredissolved in DCM (10 mL)
  6. washThe solution was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-6fc950e5ffea42a291d4f77f23318e56
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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