Sodium Bicarbonate → HCID 178433845, Verbindung

3′-Amino-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid hydrochloride 11f (287 mg, 1.03 mmol) was dissolved in 3.5 mL of hydrochloric acid (1 N) upon cooling by an ice-water bath, followed by dropwise addition of 1.5 mL of aqueous sodium nitrite (78 mg, 1.13 mmol). After the mixture was stirred for 20 minutes, 2-(2,3-dihydro-benzofuran-5-yl)-5-methyl-2,4-dihydro-pyrazol-3-one 7c (200 mg, 0.93 mmol) was added. The mixture was adjusted to pH 8-9 by batch addition of aqueous sodium bicarbonate (1.298 g, 15.45 mmol). The generated bubbles were quenched with 2 mL of ethanol. The mixture was warmed up to room temperature and reacted overnight. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was filtered and then the filter cake was dissolved in 20 mL of water. After mixing well, the mixture was adjusted to pH 3˜4 with concentrated hydrochloric acid, filtered and dried. The residue was washed with 10 mL of the solvent mixture of dichloromethane/methanol (V:V=1:1), and then the crude product was purified by HPLC to obtain the title compound 3′-{N′-[1-(2,3-dihydro-benzofuran-5-yl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]-hydrazino}-2′-hydroxy-5′-methyl-biphenyl-3-carboxylic acid 13 (100 mg, yield 23.0%) as a red solid.

1. temperatureupon cooling by an ice-water bath
2. customThe generated bubbles were quenched with 2 mL of ethanol
3. customreacted overnight
4. filtrationThe mixture was filtered
5. dissolutionthe filter cake was dissolved in 20 mL of water
6. additionAfter mixing well
7. filtrationfiltered
8. customdried
9. washThe residue was washed with 10 mL of the solvent mixture of dichloromethane/methanol (V:V=1:1)
10. customthe crude product was purified by HPLC

ORD-Eintrag

ord-d70cd3354ecd49b6b98f9bc5f08c1a1f

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367710B2