Propanedioic acid, monoethyl ester → HCID 86724156, compound

HRID 1748834Notes

Reaction equation

HRID 1748834 reaction equation
Cl[C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1[CH:14]([C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1[CH3:31])[CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18].[K].[CH2:33]([O:35][C:36]([CH2:38]C([O-])=O)=[O:37])[CH3:34].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>CN(C)C1C=CN=CC=1.C([Pd]Cl)C=C>[CH2:33]([O:35][C:36](=[O:37])[CH2:38][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1[CH:14]([C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1[CH3:31])[CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH3:34]

Participants

7

Reactant 4

HCID 3595298Propanedioic acid, monoethyl esterHCID 5462222PotassiumHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86724155HCID 86724155, compound

Product 1

HCID 86724156HCID 86724156, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 178455862HCID 178455862, compoundCatalyst

Procedure

A flask was charged with methyl 4-(1-(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-methoxy-4-oxobutyl)-3-methylbenzoate (2.20 g, 4.98 mmol), potassium; ethoxycarbonyl-acetate (1.70 g, 9.96 mmol), N,N-dimethylpyridin-4-amine (0.608 g, 4.98 mmol), dicyclohexyl-(2′,6′-diisopropoxy-biphenyl-2-yl)-phosphane (0.836 g, 1.79 mmol) and allylpalladium(II) chloride (0.219 g, 0.597 mmol). The flask was evacuated and backfilled with Argon. Mesitylene (13.2 mL) was added then the mixture was stirred at rt for about 10 min under Argon. The mixture was heated at about 120° C. for about 16 h, allowed to cool to rt then filtered. The filter cake was rinsed with EtOAc (20 mL). The filtrate was concentrated in vacuo. The residue was semi-purified by column chromatography (SiO2, 10-30% EtOAc/heptane) to give crude methyl 4-(1-(5-(2-ethoxy-2-oxoethyl)-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)-4-methoxy-4-oxobutyl)-3-methylbenzoate (1.23 g, 50%). The material was used as such in the next step: LC-MS (Table 1, Method g) Rt=2.44 min, m/z 494 (M+H)+.

Workup

  1. customThe flask was evacuated
  2. additionMesitylene (13.2 mL) was added
  3. temperatureThe mixture was heated at about 120° C. for about 16 h
  4. temperatureto cool to rt
  5. filtrationthen filtered
  6. washThe filter cake was rinsed with EtOAc (20 mL)
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-d8035aebfcc0483aa3ee400009008c2e
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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