1,2-Dimethoxyethane → 5-[2-(Acetoxymethyl)-3-(4-methyl-5-oxo-6-{[4-(piperidin-4-yl)phenyl]-amino}-4,5-dihydropyrazin-2-yl)phenyl]-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-6-one

HRID 1918841Notes

Reaction equation

HRID 1918841 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:21]1[CH2:26][CH2:25][C:24]2[C:27]3[CH2:33][CH2:32][CH2:31][CH2:30][C:28]=3[S:29][C:23]=2[C:22]1=[O:34])(=[O:3])[CH3:2].Br[C:36]1[N:41]=[C:40]([NH:42][C:43]2[CH:48]=[CH:47][C:46]([CH:49]3[CH2:54][CH2:53][N:52](C(OC(C)(C)C)=O)[CH2:51][CH2:50]3)=[CH:45][CH:44]=2)[C:39](=[O:62])[N:38]([CH3:63])[CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(OCC)(=O)C>[C:1]([O:4][CH2:5][C:6]1[C:11]([C:36]2[N:41]=[C:40]([NH:42][C:43]3[CH:44]=[CH:45][C:46]([CH:49]4[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]4)=[CH:47][CH:48]=3)[C:39](=[O:62])[N:38]([CH3:63])[CH:37]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:21]1[C:22](=[O:34])[C:23]2[S:29][C:28]3[CH2:30][CH2:31][CH2:32][CH2:33][C:27]=3[C:24]=2[CH2:25][CH2:26]1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580437182-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl AcetateHCID 58043998tert-Butyl 4-(4-(6-Bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)piperidine-1-carboxylate

Product 1

HCID 670162355-[2-(Acetoxymethyl)-3-(4-methyl-5-oxo-6-{[4-(piperidin-4-yl)phenyl]-amino}-4,5-dihydropyrazin-2-yl)phenyl]-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-6-oneYield 125.4%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A 10 mL microwave vial with a magnetic stirrer was charged with 111a (173 mg, 0.36 mmol), 121a (139 mg, 0.3 mmol), 1M sodium carbonate solution (1.2 mL, 1.2 mmol) and 1,2-dimethoxyethane (3 mL). After bubbling nitrogen through the resulting suspension for 10 min, tetrakis(triphenylphosphine)-palladium(0) (18 mg, 0.015 mmol) was added. The reaction mixture was heated at 130° C. for 15 minutes in the microwave reactor. After this time, ethyl acetate (15 mL) and water (10 mL) were added, and the layers were separated. The aqueous layer was extracted with Ethyl acetate (2×20 mL), and the combined organic layers were washed with brine and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, ethyl acetate/hexanes) to afford compound 121b as yellow oil (240 mg).

Workup

  1. customAfter bubbling nitrogen through the resulting suspension for 10 min
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with Ethyl acetate (2×20 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customThe drying agent was removed by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by flash column chromatography (silica, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-42d1c69d7e2343d6ae21a8d76f73b441
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…