Ammonium Acetate → 1-{[3'-(1-Aminoethyl)-5'-chloro-3-fluoro-2'-methoxy-6'-methylbiphenyl-4-yl]carbonyl}azetidine-3-carbonitrile

HRID 510885Notes

Reaction equation

HRID 510885 reaction equation
[C:1]([C:4]1[C:5]([O:27][CH3:28])=[C:6]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:23][CH:22]([C:24]#[N:25])[CH2:21]3)=[O:19])=[C:14]([F:26])[CH:13]=2)[C:7]([CH3:11])=[C:8]([Cl:10])[CH:9]=1)(=O)[CH3:2].C([O-])(=O)C.[NH4+].C([BH3-])#[N:35].[Na+]>CO.C(#N)C>[NH2:35][CH:1]([C:4]1[C:5]([O:27][CH3:28])=[C:6]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:23][CH:22]([C:24]#[N:25])[CH2:21]3)=[O:19])=[C:14]([F:26])[CH:13]=2)[C:7]([CH3:11])=[C:8]([Cl:10])[CH:9]=1)[CH3:2]

Participants

6

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 866668041-[(3'-Acetyl-5'-chloro-3-fluoro-2'-methoxy-6'-methylbiphenyl-4-yl)carbonyl]azetidine-3-carbonitrile

Product 1

HCID 866668061-{[3'-(1-Aminoethyl)-5'-chloro-3-fluoro-2'-methoxy-6'-methylbiphenyl-4-yl]carbonyl}azetidine-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 1-[(3′-acetyl-5′-chloro-3-fluoro-2′-methoxy-6′-methylbiphenyl-4-yl)carbonyl]azetidine-3-carbonitrile (25 mg, 0.062 mmol), ammonium acetate (48 mg, 0.62 mmol) and sodium cyanoborohydride (8 mg, 0.1 mmol) in methanol (0.2 mL) and acetonitrile (0.2 mL) was heated at 65° C. overnight in a sealed tube. The mixture was cooled to room temperature, quenched with saturated sodium bicarbonate and extracted with dichloromethane. The combined extracts were dried over magnesium sulfate, filtered and concentrated to dryness. The resulting crude product was used directly in next step (21 mg, 84%). LCMS calculated for C21H19ClFN2O2 (M−NH2)+: m/z=385.1. found: 385.1.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customquenched with saturated sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-6c05050f8cee49989ed480960e3cd89a
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

Loading…