Water → HCID 86661723, compound

HRID 2284498Notes

Reaction equation

HRID 2284498 reaction equation
Cl[C:2]1[N:10]=[C:9]([Cl:11])[C:8]([Cl:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[OH:13][CH2:14][CH2:15][CH2:16][C:17]1([OH:20])[CH2:19][CH2:18]1.C(O[K])(C)(C)C.O>CN(C=O)C>[Cl:12][C:8]1[C:9]([Cl:11])=[N:10][C:2]([O:13][CH2:14][CH2:15][CH2:16][C:17]2([OH:20])[CH2:19][CH2:18]2)=[C:3]([CH:7]=1)[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 4

HCID 962WaterHCID 10582773HCID 10582773, compoundHCID 537509302,5,6-Trichloropyridine-3-carboxamideHCID 178418922HCID 178418922, compound

Product 1

HCID 86661723HCID 86661723, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of compound 2,5,6-trichloronicotinamide (0.6 g, 2.7 mmol), 1-(3-hydroxypropyl)cyclopropanol (370 mg, 3.2 mmol) and tert-BuOK (363 mg, 3.2 mmol) in DMF was stirred at room temperature overnight and the reaction mixture was then poured into cold water, the mixture was extracted twice with ethyl acetate, the combined organic layers were washed with brine twice, dried over Na2SO4 and concentrated, the residue was purified by column chromatography (silica gel, Petroleum ether: EtOAc=1:0 to 5:1) to give the 5,6-dichloro-2-(3-(1-hydroxycyclopropyl)propoxy)nicotinamide (0.72 g, 73%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.65 (s, 1H), 8.29 (s, 1H), 8.03 (s, 1H), 5.48 (s, 1H), 4.82 (t, 2H, J=6.4 Hz), 2.36 (m, 2H), 1.97 (m, 2H), 0.94 (t, 2H), 0.73 (t, 2H).

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate
  2. washthe combined organic layers were washed with brine twice
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customthe residue was purified by column chromatography (silica gel, Petroleum ether: EtOAc=1:0 to 5:1)

Sources & evidence

ORD record
ord-d07dc308ae21410f9446de8e0e88d520
Source dataset
uspto-grants-2015_09
Patent number
US09145429B2

Reaction notes

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