Sodium Iodide → HCID 178457798, compound

HRID 518725Notes

Reaction equation

HRID 518725 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:29]=[CH:28][C:27]([CH2:30]O)=[CH:26][C:12]=3[N:13]\2[C@H:14]2[CH2:19][CH2:18][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:38]1[CH:42]=[N:41][CH:40]=[N:39]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(Cl)Cl>[N:38]1([CH2:30][C:27]2[CH:28]=[CH:29][C:11]3[NH:10]/[C:9](=[N:8]\[C:6](=[O:7])[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:33][CH:32]=4)/[N:13]([C@H:14]4[CH2:15][CH2:16][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:19]4)[C:12]=3[CH:26]=2)[CH:42]=[N:41][CH:40]=[N:39]1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 178457799HCID 178457799, compound

Product 1

HCID 178457798HCID 178457798, compoundYield 31.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. cooled solution of (E)-4-fluoro-N-(6-(hydroxymethyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (100 mg, 0.221 mmol) in DCM (2.5 mL) was added thionyl chloride (0.081 mL, 1.105 mmol) dropwise, and the reaction was stirred at 0° C. for 30 minutes. The solvent was removed at reduced pressure, and the residue was dried in vacuo for 5 minutes. The residue was resuspended in ACN (2 mL), cooled to 0° C., and 1H-1,2,4-triazole (153 mg, 2.210 mmol), potassium carbonate (305 mg, 2.210 mmol), and sodium iodide (33.1 mg, 0.221 mmol) were added. The reaction was stirred at RT. After 16 hours, the solvent was removed, and the residue was partitioned between water and DCM. The aqueous layer was neutralized (pH approximately 8) with 2 N aqueous HCl and extracted with DCM. The combined organic layers were concentrated, adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-10% MeOH in DCM, to provide (E)-N-(6-((1H-1,2,4-triazol-1-yl)methyl)-1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-4-fluorobenzamide (35 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.80 (s, 1H), 8.69 (s, 1H), 8.33 (dd, J=6.0, 8.6 Hz, 2H), 7.95 (s, 1H), 7.76 (s, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.24 (dd, J=8.8 Hz, 8.8 Hz, 2H), 7.15, (d, J=8.2 Hz, 1H), 5.45 (s, 2H), 4.78 (brs, 1H), 4.02-4.14 (m, 1H), 2.74-2.85 (m, 2H), 2.54 (brs, 1H), 2.10-2.13 (d, J=12.8 Hz, 2H), 1.69-1.76 (m, 2H), 1.59-1.62 (m, 2H), 1.11 (d, J=6.6 Hz, 6H). MS, m/z (C27H30FN7O2): calcd, 503.2; found, 503.7 [M+H].

Workup

  1. customThe solvent was removed at reduced pressure
  2. customthe residue was dried in vacuo for 5 minutes
  3. temperaturecooled to 0° C.
  4. stirringThe reaction was stirred at RT
  5. waitAfter 16 hours
  6. customthe solvent was removed
  7. customthe residue was partitioned between water and DCM
  8. extractionextracted with DCM
  9. concentrationThe combined organic layers were concentrated
  10. custompurified by column chromatography
  11. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-d6b52b39c14843ba9425149a3defcb6a
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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