3-Hydroxybenzoic Acid → HCID 10311619, compound

HRID 354097Notes

Reaction equation

HRID 354097 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](O)=[O:6].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[CH2:34]([O:36][C:37](=[O:63])[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][C:45]2[C:50]([C:51](=[O:62])[NH:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([CH2:60][NH2:61])=[CH:56][CH:55]=3)=[CH:49][CH:48]=[CH:47][N:46]=2)[CH:39]=1)[CH3:35].CN1CCOCC1>CN(C)C=O>[CH2:34]([O:36][C:37](=[O:63])[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][C:45]2[C:50]([C:51](=[O:62])[NH:52][CH2:53][C:54]3[CH:55]=[CH:56][C:57]([CH2:60][NH:61][C:5](=[O:6])[C:4]4[CH:8]=[CH:9][CH:10]=[C:2]([OH:1])[CH:3]=4)=[CH:58][CH:59]=3)=[CH:49][CH:48]=[CH:47][N:46]=2)[CH:39]=1)[CH3:35]

Participants

7

Reactant 5

HCID 74203-Hydroxybenzoic AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69933182HCID 69933182, compound

Product 1

HCID 10311619HCID 10311619, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Hydroxy-benzoic acid (27 mg, 0.19 mmol), 1-hydroxybenzotriazole (31 mg, 0.23 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (45 mg, 0.23 mmol) were added to a solution of 3-[3-(4-aminomethyl-benzylcarbamoyl)-pyridin-2-yloxy]-benzoic acid ethyl ester hydrochloride (100 mg, 0.19 mmol) (see Preparation 9) and N-methyl morpholine (0.11 ml, 0.97 mmol) in N,N-dimethylformamide (15 ml). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours, concentrated in vacuo and the residue partitioned between dichloromethane (20 ml) and water (20 ml). The organic phase was separated, washed with a saturated aqueous solution of sodium chloride (20 ml), dried over anhydrous magnesium sulphate and concentrated under reduced pressure. The residue was then purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 changing to 98:1, by volume) giving 3-(3-{4-[(3-hydroxy-benzoylamino)-methyl]-benzylcarbamoyl}-pyridin-2-yloxy)-benzoic acid ethyl ester (45 mg) as an off-white foam.

Workup

  1. concentrationconcentrated in vacuo
  2. customthe residue partitioned between dichloromethane (20 ml) and water (20 ml)
  3. customThe organic phase was separated
  4. washwashed with a saturated aqueous solution of sodium chloride (20 ml)
  5. dry with materialdried over anhydrous magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol (99:1 changing to 98:1, by volume)

Sources & evidence

ORD record
ord-1bcd31ca492d430fb96a981cffca67d1
Source dataset
uspto-grants-2004_06
Patent number
US06756392B2

Reaction notes

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