2-Hydroxy-p-toluic acid → HCID 22058432, compound

HRID 497516Notes

Reaction equation

HRID 497516 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=O.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[F:36][C:37]1[CH:38]=[N:39][C:40]([O:52][C:53]2[CH:58]=[CH:57][C:56]([F:59])=[CH:55][CH:54]=2)=[C:41]([CH:51]=1)[C:42]([NH:44][CH:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)=[O:43].CN1CCOCC1>CN(C)C=O>[F:36][C:37]1[CH:38]=[N:39][C:40]([O:52][C:53]2[CH:58]=[CH:57][C:56]([F:59])=[CH:55][CH:54]=2)=[C:41]([CH:51]=1)[C:42]([NH:44][CH:45]1[CH2:46][CH2:47][N:48]([C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=2[OH:11])[CH2:49][CH2:50]1)=[O:43]

Participants

7

Reactant 5

HCID 57882-Hydroxy-p-toluic acidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22058437HCID 22058437, compound

Product 1

HCID 22058432HCID 22058432, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methylsalicylic acid (91 mg, 0.595 mmol), 1-hydroxybenzotriazole hydrate (110 mg, 0.811 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (135 mg, 0.703 mmol), 5-fluoro-2-(4-fluoro-phenoxy)-N-piperidin-4-yl-nicotinamide hydrochloride (200 mg, 0.541 mmol) (see Preparation 29) and N-methyl morpholine (0.12 ml, 1.08 mmol) were stirred in N,N-dimethylformamide (4 ml) under an atmosphere of nitrogen at room temperature for 18 hours. The reaction mixture was then partitioned between ethyl acetate (10 ml) and water (10 ml), the organic layer separated, washed with a saturated aqueous solution of sodium chloride (10 ml) and dried over anhydrous magnesium sulphate. The solvent was then removed in vacuo and the residue purified via flash column chromatography on silica gel eluting with a solvent gradient of 100% dichloromethane changing to 99:1, by volume, dichloromethane:methanol. The resulting white foam was triturated with pentane (5 ml) giving 5-fluoro-2-(4-fluoro-phenoxy)-N-[1-(2-hydroxy-4-methyl-benzoyl)-piperidin-4-yl]-nicotinamide (169 mg) as a white solid.

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate (10 ml) and water (10 ml)
  2. customthe organic layer separated
  3. washwashed with a saturated aqueous solution of sodium chloride (10 ml)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. customThe solvent was then removed in vacuo
  6. customthe residue purified via flash column chromatography on silica gel eluting with a solvent gradient of 100% dichloromethane changing to 99:1, by volume, dichloromethane
  7. customThe resulting white foam was triturated with pentane (5 ml)

Sources & evidence

ORD record
ord-cc238f2bfac6458cb3ca1577b240e1f8
Source dataset
uspto-grants-2005_09
Patent number
US06949573B2

Reaction notes

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