Hydrochloric Acid → 1-(4-chloro-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide

HRID 384978Notes

Reaction equation

HRID 384978 reaction equation
N[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][CH:6]2[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([NH:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)=[O:18])[C:12]1=[O:26].N([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[ClH:37]>O.Cl[Cu]>[Cl:37][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][CH:6]2[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([NH:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)=[O:18])[C:12]1=[O:26]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 23668193Sodium NitriteHCID 498038671-(4-amino-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 498038691-(4-chloro-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent3×

Procedure

To a mixture of 1-(4-amino-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide (600 mg, 1.0 eq) in H2O (4 mL) and conc. HCl (2 mL) was added dropwise NaNO2 (1.1 eq) in H2O (1 mL) at 0° C., the mixture was stirred at room temperature for 30 minutes. Then this mixture was added to another flask containing CuCl (1.5 eq), 2 mL H2O and 1 mL aqueous HCl at 0° C., the mixture was stirred for 5 h. At the end of reaction, saturated Na2CO3 aqueous was added to adjust to pH 12. The aqueous solution was extracted with ethyl acetate three times. The combined organic layer was washed with brine and dried over MgSO4, evaporated the filtrate to give the crude product, which was purified by Flash Column (DCM:MeOH=30:1) to afford 1-(4-chloro-2,3-dihydro-1H-inden-1-yl)-2-oxo-N-(pyridin-4-yl)-1,2-dihydropyridine-3-carboxamide (350 mg, 55%). MS (ESI) 366.0 (M+H); 1H NMR (300 MHz, CDCl3) δ 12.31 (s, 1H), 8.61 (bd, 1H), 8.53 (bs, 2H), 7.69 (bs, 2H), 7.38 (bd, 1H), 7.26 (bm, 2H), 7.03 (d, J=6.0 Hz, 2H), 6.69 (bs, 1H), 6.46 (bs, 1H), 3.05-3.25 (bm, 2H), 2.91 (bd, 1H), 2.08 (bd, 1H).

Workup

  1. additionThen this mixture was added to another flask
  2. stirringthe mixture was stirred for 5 h
  3. additionwas added
  4. extractionThe aqueous solution was extracted with ethyl acetate three times
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated the filtrate
  8. customto give the crude product, which
  9. customwas purified by Flash Column (DCM:MeOH=30:1)

Sources & evidence

ORD record
ord-020bfa2dde35495d99698ba4a4930689
Source dataset
uspto-grants-2013_02
Patent number
US08367836B2

Reaction notes

Loading…