1,2-Dimethoxyethane → HCID 68096893, compound

HRID 1918965Notes

Reaction equation

HRID 1918965 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)=[N:3]1.[C:26]([O:29][CH2:30][C:31]1[C:36]([N:37]2[CH2:48][CH2:47][N:46]3[C:39](=[CH:40][C:41]4[CH2:42][C:43]([CH3:50])([CH3:49])[CH2:44][C:45]=43)[C:38]2=[O:51])=[CH:35][C:34]([F:52])=[CH:33][C:32]=1Br)(=[O:28])[CH3:27].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.CCOC(C)=O>[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=[C:13]([C:32]3[C:31]([CH2:30][O:29][C:26](=[O:28])[CH3:27])=[C:36]([N:37]4[CH2:48][CH2:47][N:46]5[C:39](=[CH:40][C:41]6[CH2:42][C:43]([CH3:49])([CH3:50])[CH2:44][C:45]=65)[C:38]4=[O:51])[CH:35]=[C:34]([F:52])[CH:33]=3)[CH:14]=2)=[N:3]1

Participants

10

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580441963-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 670163042-Bromo-4-fluoro-6-(9-oxo-4,4-dimethyl-1,10diazatricyclo[6.4.0.02,6]-dodeca-2(6),7-dien-10-yl)benzyl Acetate

Product 1

HCID 68096893HCID 68096893, compoundYield 88.6%

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 196a (450 mg, 1.3 mmol), 189a (240 mg, 0.5 mmol), DME (4 mL) and 1M aqueous sodium carbonate (1.5 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 10 min. After this time, EtOAc (5 mL) and water (5 mL) were added. The separated aqueous layer was extracted with EtOAc (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 83% yield (260 mg) of 196b.

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 EtOAc (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-a6717f9fb4364faca86ef025c4d990d0
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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