Potassium Phosphate, Tribasic → 2-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamide

HRID 62527

Reaction equation

HRID 62527 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8](I)[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[NH2:11][C:12]1[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=1[C:14]([NH:16]OC)=[O:15].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:31]1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC(O)=O.CC(O)=O.[Pd]>[Cl:1][C:2]1[CH:9]=[C:8]([NH:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([NH:16][CH3:31])=[O:15])[C:5]([C:6]#[N:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 123927072-Amino-N-methoxybenzamideHCID 575169126-Chloro-4-iodopyridine-3-carbonitrile

Product 1

HCID 575169132-(2-Chloro-5-cyanopyridin-4-ylamino)-N-methylbenzamideYield 740.3%

Reagents, catalysts & solvents 2

HCID 4144353Palladium (II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-chloro-4-iodo-nicotinonitrile (14 g, 53.03 mmole, 1 eq), 2-amino-N-methoxy-benzamide (7.96 g, 53.03 mmole, 1 eq) and K3PO4 (28.14 g, 132.57 mmole, 2.5 eq) in 1,4-dioxane (250 mL) was degassed with N2 for 1 h. To this mixture were added Pd(OAC)2 (0.238 g, 1.06 mmole, 0.02 eq) and DPEPhos (2.28 g, 4.24 mmole, 0.08 eq). The resulting reaction mixture was degassed with N2 for another 15 min after which the resulting reaction mixture was stirred at 110° C. overnight. After completion of reaction solid material was collected by filtration, dissolved in water (500 mL), and extracted with ethyl acetate (5×200 mL). Combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude material. It was purified by column chromatography over silica gel (60-120 mesh) using 0.2% methanolic ammonia (10% ammonia in MeOH) in dichloromethane as the eluant to give the title compound as a pale yellow solid (9 g, 59%). 1H-NMR (400 MHz, DMSO-d6): δ 2.75 (d, 3H, J=4.56 Hz), 7.09 (s, 1H), 7.25-7.35 (m, 1H), 7.53-7.60 (m, 2H), 7.72 (d, 1H, J=7.48 Hz), 8.56 (s, 1H), 8.69-8.79 (brs, 1H), 10.65 (s, 1H). LC-MS calculated for C14H11ClN4O (M+H) 287.06, found 286.9.

Workup

  1. customwas degassed with N2 for 1 h
  2. customThe resulting reaction mixture
  3. customwas degassed with N2 for another 15 min after which
  4. customthe resulting reaction mixture
  5. customAfter completion of reaction solid material
  6. filtrationwas collected by filtration
  7. dissolutiondissolved in water (500 mL)
  8. extractionextracted with ethyl acetate (5×200 mL)
  9. dry with materialCombined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto give crude material
  13. customIt was purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-13f3d4ff92934fd497c45693bab99090
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Linked notes

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