Hydrochloric Acid → HCID 178436722, compound

HRID 1192517Notes

Reaction equation

HRID 1192517 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:24](O)=[O:25])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:6](/[N:10]=[N:11]/[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:7]=1[C:8]#[CH:9].C(N(CC)C(C)C)(C)C.Cl.[CH3:37][NH:38][O:39][CH3:40].Cl>CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:24]([N:38]([O:39][CH3:40])[CH3:37])=[O:25])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:6](/[N:10]=[N:11]/[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[C:7]=1[C:8]#[CH:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 178436724HCID 178436724, compound

Product 1

HCID 178436722HCID 178436722, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 4-chloro-6-[(1E)-3,3-diethyltriaz-l-en-l-yl]-5-ethynyl-3′-fluorobiphenyl-2-carboxylic acid (2.7 g, 7.1 mmol) in N,N-dimethylformamide (14 mL) was treated with N,N-diisopropylethylamine (4.3 mL, 25 mmol) followed by O-(benzotriazol-1-yl)-N,N,N,′N′-tetramethyluronium hexafluorophosphate (3.5 g, 9.3 mmol) and stirred at 20° C. for 5 minutes. The reaction mixture was treated with N,O-dimethylhydroxylamine hydrochloride (0.9 g, 9.3 mmol) and stirred at 20° C. for 1 hour. The reaction mixture was poured into 0.5 M hydrogen chloride in water (100 mL) and extracted with ethyl acetate (150 mL). The organic layer was washed with saturated sodium bicarbonate (50 mL), brine (25 mL), dried with sodium sulfate, filtered, and concentrated to a crude residue. Purification by flash column chromatography using ethyl acetate in hexanes (0%-40%) gave the desired product (2.7 g, 92% for 2 steps). LCMS for C21H23ClFN4O2 (M+H)+: m/z=417.1; Found: 417.0.

Workup

  1. stirringstirred at 20° C. for 1 hour
  2. extractionextracted with ethyl acetate (150 mL)
  3. washThe organic layer was washed with saturated sodium bicarbonate (50 mL), brine (25 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a crude residue
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-8bd4b55900404fd191d7f5e470cfbecd
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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