Potassium Phosphate, Tribasic → 4-(5-Cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acid

HRID 81078Notes

Reaction equation

HRID 81078 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)[CH:5]=[C:4]([S:17][CH3:18])[C:3]=1[C:19]#[N:20].[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[CH:29]=[C:28](B(O)O)[CH:27]=[CH:26]2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C(=O)C.CCOC(C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:19]([C:3]1[C:4]([S:17][CH3:18])=[CH:5][C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=2)=[N:7][C:2]=1[C:28]1[CH:27]=[CH:26][C:25]2[C:30](=[CH:31][CH:32]=[C:23]([O:22][CH3:21])[CH:24]=2)[CH:29]=1)#[N:20]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 46416926-Methoxy-2-naphthaleneboronic acidHCID 866656994-(6-Chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid

Product 1

HCID 669269734-(5-Cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acidYield 64.3%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 4-(6-chloro-5-cyano-4-(methylthio)pyridin-2-yl)benzoic acid (50 mg, 0.164 mmol) and 6-methoxynaphthalen-2-ylboronic acid (49.7 mg, 0.246 mmol), potassium phosphate (139 mg, 0.656 mmol) and palladium tetrakis(triphenylphosphine) (18.96 mg, 0.016 mmol) in N,N-dimethylacetamide (2 mL) was pumped under vacuum and backfilled with nitrogen three times. After 2 h at 100° C., the mixture was cooled to room temperature, diluted with EtOAc (60 mL), washed with saturated NH4Cl (5 mL), water (5 ml), brine (5 mL), dried (MgSO4) and concentrated. The residue was triturated with MeOH (10 ml) and filtered. The yellow solid was collected and dried under vacuum to give 4-(5-cyano-6-(6-methoxynaphthalen-2-yl)-4-(methylthio)pyridin-2-yl)benzoic acid (45 mg, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.34-8.53 (2H, m), 8.21-8.34 (1H, m), 7.99-8.19 (4H, m), 7.85-7.98 (1H, m), 7.41-7.54 (1H, m), 7.18-7.37 (2H, m), 3.94 (3H, s); MS (ES+) m/z: 427 (M+H); LC retention time: 4.01 min (analytical HPLC Method A).

Workup

  1. washwashed with saturated NH4Cl (5 mL), water (5 ml), brine (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was triturated with MeOH (10 ml)
  5. filtrationfiltered
  6. customThe yellow solid was collected
  7. customdried under vacuum

Sources & evidence

ORD record
ord-05176bd0a2e54b849d7ebc12a89cb60a
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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