Thionyl Chloride → HCID 178454568, compound

HRID 518751

Reaction equation

HRID 518751 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]([NH:20][C:21](=[O:25])[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[CH2:43][CH2:42][CH:41]([C:44]([OH:47])([CH3:46])[CH3:45])[CH2:40][CH2:39]1>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][N:38]4[CH2:43][CH2:42][CH:41]([C:44]([OH:47])([CH3:46])[CH3:45])[CH2:40][CH2:39]4)=[CH:26][C:12]=3[N:13]\2[C@H:14]2[CH2:15][CH2:16][C@@H:17]([NH:20][C:21](=[O:25])[CH:22]([CH3:23])[CH3:24])[CH2:18][CH2:19]2)=[O:7])=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 52003212-(4-Piperidyl)-2-propanolHCID 178454569HCID 178454569, compound

Product 1

HCID 178454568HCID 178454568, compoundYield 31.3%

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-isobutyramidocyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide (75 mg, 0.166 mmol) in DCM (5 mL) was added thionyl chloride (0.060 mL, 0.829 mmol) dropwise. The resulting mixture was stirred at 0° C. for 30 minutes. After 30 minutes, the solvent was removed, and the residue was suspended in ACN (5 mL) and re-concentrated to remove residual thionyl chloride. The residue was resuspended in ACN (3 mL), cooled to 0° C., and 2-(piperidin-4-yl)propan-2-ol (95 mg, 0.663 mmol) was added. The reaction was stirred overnight at RT. After 16 hours, the reaction mixture was concentrated and partitioned between EtOAc and water. The organic layer was concentrated and the residue was purified by column chromatography, eluting with 0-100% (90:9:1 DCM/MeOH/NH4OH) in DCM to provide (E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-(cis-4-isobutyramidocyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide as a white powder (30 mg, 31.3% yield). MS, m/z (C33H44FN5O3): calcd, 577.3. found, 578.1 [M+H].

Workup

  1. waitAfter 30 minutes
  2. customthe solvent was removed
  3. concentrationre-concentrated
  4. customto remove residual thionyl chloride
  5. temperaturecooled to 0° C.
  6. stirringThe reaction was stirred overnight at RT
  7. waitAfter 16 hours
  8. concentrationthe reaction mixture was concentrated
  9. custompartitioned between EtOAc and water
  10. concentrationThe organic layer was concentrated
  11. customthe residue was purified by column chromatography
  12. washeluting with 0-100% (90:9:1 DCM/MeOH/NH4OH) in DCM

Sources & evidence

ORD record
ord-77d152d1c21d4148a2c29ee72742067f
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Linked notes

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