Hydrochloric Acid → 2-[1-Benzyl-4-(4-chlorophenyl)-3,6-dimethyl-7-oxo-pyrrolo[2,3-c]pyridin-5-yl]-2-tert-butoxy-acetic acid

HRID 1473204Notes

Reaction equation

HRID 1473204 reaction equation
[CH2:1]([N:8]1[C:12]2[C:13](=[O:35])[N:14]([CH3:34])[C:15]([CH:24]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:25]([O:27]C)=[O:26])=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:11]=2[C:10](Br)=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Na+].[Na+].[Li+].[OH-].Cl>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[C:12]2[C:13](=[O:35])[N:14]([CH3:34])[C:15]([CH:24]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[C:25]([OH:27])=[O:26])=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:11]=2[C:10]([CH3:37])=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 574072TrimethylboroxineHCID 89462647methyl 2-(1-benzyl-3-bromo-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate

Product 1

HCID 715382162-[1-Benzyl-4-(4-chlorophenyl)-3,6-dimethyl-7-oxo-pyrrolo[2,3-c]pyridin-5-yl]-2-tert-butoxy-acetic acidYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of the methyl 2-(1-benzyl-3-bromo-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetate (15 mg, 0.026 mmol), trimethylboroxine (3.65 μL, 0.026 mmol) and Na2CO3 (5.56 mg, 0.052 mmol) in N,N-Dimethylformamide (DMF) (1 mL), was degassed with N2 for 5 minutes. Palladium tetrakis (3.03 mg, 2.62 μmol) was added and the mixture was degassed again with N2 for 5 minutes. The mixture was irradiated in the microwave at 140° C. for 30 minutes. The mixture was diluted with Methanol (1.000 mL), and Tetrahydrofuran (THF) (1.000 mL), treated with 2M LiOH (1 mL, 2.000 mmol) and then stirred at room temperature overnight. The mixture was treated with HCl (1M) until pH<2 and extracted with ethyl acetate. The combined extracts were concentrated and purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(1-benzyl-4-(4-chlorophenyl)-3,6-dimethyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-(tert-butoxy)acetic acid (4.0 mg, 0.007 mmol, 30% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.63-7.57 (m, 1H), 7.49-7.41 (m, 2H), 7.38-7.29 (m, 6H), 6.81 (s, 1H), 5.81 (s, 2H), 5.18 (s, 1H), 3.67 (s, 3H), 1.44 (s, 3H), 1.07 (s, 9H); LCMS (m/z) ES+=493 (M+1).

Workup

  1. customwas degassed with N2 for 5 minutes
  2. customthe mixture was degassed again with N2 for 5 minutes
  3. customThe mixture was irradiated in the microwave at 140° C. for 30 minutes
  4. additionThe mixture was diluted with Methanol (1.000 mL), and Tetrahydrofuran (THF) (1.000 mL)
  5. extractionextracted with ethyl acetate
  6. concentrationThe combined extracts were concentrated
  7. custompurified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-298ac258cead4070ab632c7c7cbfdc86
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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