Nicotinic Acid → HCID 44632659, compound

HRID 2362031Notes

Reaction equation

HRID 2362031 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C.Cl.[Cl:40][C:41]1[CH:42]=[C:43]([C:48]2[CH:52]([CH2:53][NH2:54])[CH2:51][O:50][N:49]=2)[CH:44]=[CH:45][C:46]=1[Cl:47].[OH-].[Na+]>CN(C=O)C.O>[Cl:40][C:41]1[CH:42]=[C:43]([C:48]2[CH:52]([CH2:53][NH:54][C:1](=[O:9])[C:2]3[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=3)[CH2:51][O:50][N:49]=2)[CH:44]=[CH:45][C:46]=1[Cl:47]

Participants

9

Reactant 6

HCID 938Nicotinic AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68552162HCID 68552162, compound

Product 1

HCID 44632659HCID 44632659, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of nicotinic acid (1 eq) in DMF (13 vol) was added HOBt (1.2 eq) and EDC.HCl (1.2 eq) at room temperature. To this mixture was added the free-based (using triethylamine (1.1 eq)) salt of C-[3-(3,4-dichloro-phenyl)-4,5-dihydro-isoxazol-4-yl]-methylamine hydrochloride (1 eq) in DMF (10 vol) and the reaction was stirred at room temperature for 18 hours. Water (100 vol) was added and the pH adjusted to 12 using 2N NaOH. The oily precipitation was extracted with EtOAc (2×67 vol). The organic phases were combined and washed with water (3×67 vol), brine (1×67 vol), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash column chromatography (eluent: EtOAc:heptane) to yield N-[3-(3,4-Dichloro-phenyl)-4,5-dihydro-isoxazol-4-ylmethyl]-nicotinamide.

Workup

  1. customThe oily precipitation
  2. extractionwas extracted with EtOAc (2×67 vol)
  3. washwashed with water (3×67 vol), brine (1×67 vol)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography (eluent: EtOAc:heptane)

Sources & evidence

ORD record
ord-da74227dc8034148abf6086e3c06cbfe
Source dataset
uspto-grants-2014_04
Patent number
US08691824B2

Reaction notes

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