1,2-Dichloroethane → HCID 178457801, compound

HRID 518745Notes

Reaction equation

HRID 518745 reaction equation
[CH:1]([NH:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[CH:19]=[C:18]([N:20]3[CH:24]=[N:23][CH:22]=[N:21]3)[CH:17]=[CH:16][C:15]=2[N+:25]([O-])=O)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].O.O.[Sn](Cl)Cl.[F:33][C:34]1[CH:44]=[CH:43][C:37]([C:38]([N:40]=[C:41]=S)=[O:39])=[CH:36][CH:35]=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CCO>[F:33][C:34]1[CH:35]=[CH:36][C:37]([C:38](/[N:40]=[C:41]2\[NH:25][C:15]3[CH:16]=[CH:17][C:18]([N:20]4[CH:24]=[N:23][CH:22]=[N:21]4)=[CH:19][C:14]=3[N:13]\2[C@H:10]2[CH2:11][CH2:12][C@@H:7]([C:5](=[O:6])[NH:4][CH:1]([CH3:3])[CH3:2])[CH2:8][CH2:9]2)=[O:39])=[CH:43][CH:44]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 61436Stannous chloride dihydrate2×HCID 81531DiisopropylethylamineHCID 2490894-Fluorobenzoyl isothiocyanateHCID 178457847HCID 178457847, compound

Product 1

HCID 178457801HCID 178457801, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of cis-N-isopropyl-4-(2-nitro-5-(1H-1,2,4-triazol-1-yl)phenylamino)-cyclohexanecarboxamide (100 mg, 0.269 mmol) in EtOH (3 mL) was added tin(II) chloride dihydrate (242 mg, 1.074 mmol). The reaction was stirred at 80° C. After 3 hours, another four equivalents of tin(II) chloride dihydrate (242 mg, 1.074 mmol) was added, and the reaction was stirred at 80° C. for an additional 3 hours, and then at RT overnight. The reaction mixture was concentrated, and the residue was partitioned between EtOAc and 1 N aqueous sodium hydroxide. The aqueous layer was extracted with EtOAc; the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The diamine was dissolved in THF (3 mL), cooled to 0° C., and 4-fluorobenzoyl isothiocyanate (53.5 mg, 0.296 mmol) was added. The reaction was stirred at 0° C. for 30 minutes, then DIPEA (0.070 mL, 0.403 mmol) and EDC (77 mg, 0.403 mmol) were added, and the reaction was stirred for 1 hour at 60° C. The residual material was concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 20-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(1H-1,2,4-triazol-1-yl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as an off-white powder (44 mg, 33.5% yield). MS, m/z (C26H28FN7O2): Calc'd, 489.2. found, 489.9 [M+H].

Workup

  1. stirringthe reaction was stirred at 80° C. for an additional 3 hours
  2. customat RT
  3. customovernight
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was partitioned between EtOAc and 1 N aqueous sodium hydroxide
  6. extractionThe aqueous layer was extracted with EtOAc
  7. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe diamine was dissolved in THF (3 mL)
  11. temperaturecooled to 0° C.
  12. stirringThe reaction was stirred at 0° C. for 30 minutes
  13. stirringthe reaction was stirred for 1 hour at 60° C
  14. concentrationThe residual material was concentrated
  15. custompurified by column chromatography
  16. washeluting with 20-100% EtOAc in DCM

Sources & evidence

ORD record
ord-060955deecd848269f06dda50457e043
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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