1,2-Dimethoxyethane → HCID 67016278, compound

HRID 1919081Notes

Reaction equation

HRID 1919081 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C([O:20][CH2:21][C:22]1[C:27]([N:28]2[CH2:39][CH2:38][N:37]3[C:30](=[CH:31][C:32]4[CH2:33][C:34]([CH3:41])([CH3:40])[CH2:35][C:36]=43)[C:29]2=[O:42])=[CH:26][C:25]([F:43])=[CH:24][C:23]=1B1OC(C)(C)C(C)(C)O1)(=O)C.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>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.CO.C(OCC)C.O.C(OCC)(=O)C>[F:43][C:25]1[CH:24]=[C:23]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:15]=[C:14]([CH3:16])[NH:13][N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[C:22]([CH2:21][OH:20])=[C:27]([N:28]2[CH2:39][CH2:38][N:37]3[C:30](=[CH:31][C:32]4[CH2:33][C:34]([CH3:40])([CH3:41])[CH2:35][C:36]=43)[C:29]2=[O:42])[CH:26]=1

Participants

10

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580441425-Bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-oneHCID 670162322-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate

Product 1

HCID 67016278HCID 67016278, compoundYield 18.8%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A microwave tube equipped with a magnetic stirrer was charged with 5-bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 112a (150 mg, 0.5 mmol), 230a (350 mg, 0.7 mmol), 1,2-dimethoxyethane (6.4 mL) and 1M aqueous sodium carbonate (1.6 mL). After bubbling N2 for 15 min, Pd(PPh3)4 (31 mg, 0.03 mmol) was added. The mixture was heated in microwave to 130° C. for 15 min. After this time, ethyl acetate (5 mL) and water (5 mL) were added. The separated aqueous layer was extracted with ethyl acetate (2×5 mL). The combined organics were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography eluting with a gradient of methylene chloride-60:35:5 methylene chloride:diethyl ether:methanol to afford a 16% yield (50 mg) of 276a.

Workup

  1. customA microwave tube equipped with a magnetic stirrer
  2. customAfter bubbling N2 for 15 min
  3. extractionThe separated aqueous layer was extracted with ethyl acetate (2×5 mL)
  4. washThe combined organics were washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by column chromatography
  9. washeluting with a gradient of methylene chloride-60:35:5 methylene chloride

Sources & evidence

ORD record
ord-c8810bae2ac3456aace0993b6218e52c
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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