Acetic Anhydride → HCID 66926900, compound

HRID 81039Notes

Reaction equation

HRID 81039 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[NH2:12][CH2:13][C:14]1[CH:15]=[C:16]([C:20]2[C:21]([F:41])=[C:22]([C:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:30][CH:29]=3)=[CH:26][N:27]=2)[C:23]#[N:24])[CH:17]=[CH:18][CH:19]=1.[C:42](OC(=O)C)(=[O:44])[CH3:43]>ClCCl.[Cl-].[Na+].O.O>[C:23]([C:22]1[C:25]([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)=[CH:26][N:27]=[C:20]([C:16]2[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=2)[CH2:13][NH:12][C:42](=[O:44])[CH3:43])[C:21]=1[F:41])#[N:24]

Participants

7

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 131731892HCID 131731892, compound

Product 1

HCID 66926900HCID 66926900, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Hunig's base (0.045 mL, 0.256 mmol) was added to a mixture of 2-(3-(aminomethyl)phenyl)-3-fluoro-5-(4-phenoxyphenyl)isonicotinonitrile bis-HCl salt (12 mg, 0.026 mmol) and acetic anhydride (0.012 mL, 0.128 mmol) in dichloromethane (3 mL). After 1 h at room temperature, the mixture was diluted with brine (10 mL), water (10 mL) and extracted with dichloromethane (3×10 mL). The combined extracts were dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane and eluting with 50-100% ethyl acetate in hexanes, gave N-(3-(4-cyano-3-fluoro-5-(4-phenoxyphenyl)pyridin-2-yl)benzyl)acetamide as off-white solid (10.2 mg, 91% yield), 1H NMR (500 MHz, CDCl3) δ ppm 8.73 (1H, s), 7.89-7.98 (2H, m), 7.57-7.66 (2H, m), 7.47-7.55 (1H, m), 7.37-7.47 (3H, m), 7.18-7.25 (1H, m), 7.14-7.18 (2H, m), 7.12 (2H, δ, J=7.70 Hz), 5.87 (1H, br. s), 4.55 (2H, δ, J=5.77 Hz), 2.07 (3H, s); MS (ES+) m/z: 438 (M+H); LC retention time: 4.388 min (analytical HPLC Method A).

Workup

  1. extractionextracted with dichloromethane (3×10 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated
  4. washeluting with 50-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-26bae571d78b4a1c80b8603358467d29
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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