Oxalyl chloride → HCID 178491050, compound

HRID 1946245Notes

Reaction equation

HRID 1946245 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:12][CH3:13])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[N:20]1([CH2:26][C:27]2[CH:41]=[CH:40][C:30]3[NH:31][C:32]([C:34]4[C:38]([NH2:39])=[CH:37][NH:36][N:35]=4)=[N:33][C:29]=3[CH:28]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(C1C=CC(OC)=C(C=1)C(Cl)=O)#N.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C.C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:12][CH3:13])=[C:7]([CH:11]=1)[C:8]([NH:39][C:38]1[C:34]([C:32]2[NH:31][C:30]3[CH:40]=[CH:41][C:27]([CH2:26][N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)=[CH:28][C:29]=3[N:33]=2)=[N:35][NH:36][CH:37]=1)=[O:10])#[N:2]

Participants

9

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 212753225-Cyano-2-methoxybenzoyl chlorideHCID 219425685-Cyano-2-methoxybenzoic acidHCID 178508054HCID 178508054, compound

Product 1

HCID 178491050HCID 178491050, compoundYield 11.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Cyano-2-methoxy-benzoic acid (Example 1F) (40 mg, 0.22 mmol) was dissolved in DCM (5 ml) and oxalyl chloride (34.4 mg, 0.264 mmol) was then added drop wise followed by DMF (1 drop). The reaction mixture was stirred at ambient temperature for 1 hour, reduced in vacuo, then re-evaporated using toluene (×2). A mixture of 3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-ylamine (100 mg, 0.33 mmol), 5-cyano-2-methoxy-benzoyl chloride and diisopropylethylamine (1.83 μl, 0.9 mmol) in THF (5 ml) was stirred at 0° C. and then allowed to warm to room temperature over 2 hours. The reaction mixture was then concentrated in vacuo. The residue was purified by flash column chromatography SiO2, 5-7% MeOH-DCM] to give 5-cyano-2-methoxy-N-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-benzamide (12 mg). (LC/MS Acidic: Rt 2.02 min [M−H]+458).

Workup

  1. customre-evaporated
  2. stirringwas stirred at 0° C.
  3. temperatureto warm to room temperature over 2 hours
  4. concentrationThe reaction mixture was then concentrated in vacuo
  5. customThe residue was purified by flash column chromatography SiO2, 5-7% MeOH-DCM]

Sources & evidence

ORD record
ord-85a248a922774a20bb47ae4240c2ed0b
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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