Thionyl Chloride → HCID 178494484, compound

HRID 518724Notes

Reaction equation

HRID 518724 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][OH:31])=[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.[CH3:38][O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:29]=[CH:28][C:27]([CH2:30][O:31][CH3:38])=[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]([CH3:23])[CH3:24])[CH2:16][CH2:15]2)=[O:7])=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 10942334Sodium MethoxideHCID 178457799HCID 178457799, compound

Product 1

HCID 178494484HCID 178494484, compoundYield 43.6%

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 and the residue was resuspended in ACN (2 mL), cooled to 0° C., and sodium methoxide (478 mg, 2.210 mmol) was added. The reaction was stirred overnight at RT. The solvent was removed on a rotovap, and the residue was partitioned between water and DCM. The aqueous layer was neutralized (pH approximately 8) with concentrated 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)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(methoxymethyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a white powder (45 mg, 43.6% yield). MS, m/z (C26H31FN4O3): calcd, 466.2. found, 466.8 [M+H].

Workup

  1. customThe solvent was removed
  2. temperaturecooled to 0° C.
  3. stirringThe reaction was stirred overnight at RT
  4. customThe solvent was removed on a rotovap
  5. customthe residue was partitioned between water and DCM
  6. extractionextracted with DCM
  7. concentrationThe combined organic layers were concentrated
  8. custompurified by column chromatography
  9. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-fcccfc4b35c345fdbda743f299c9da01
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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