1,2-Dimethoxyethane → HCID 68096416, compound

HRID 1918927Notes

Reaction equation

HRID 1918927 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]=2)[C:3]1=[O:24].[C:25]([O:28][CH2:29][C:30]1[C:35]([N:36]2[CH2:47][CH2:46][N:45]3[C:38](=[CH:39][C:40]4[CH2:41][C:42]([CH3:49])([CH3:48])[CH2:43][C:44]=43)[C:37]2=[O:50])=[CH:34][CH:33]=[CH:32][C:31]=1Br)(=[O:27])[CH3:26].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>[C:25]([O:28][CH2:29][C:30]1[C:31]([C:6]2[CH:5]=[C:4]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][N:19]=3)[C:3](=[O:24])[N:2]([CH3:1])[CH:7]=2)=[CH:32][CH:33]=[CH:34][C:35]=1[N:36]1[CH2:47][CH2:46][N:45]2[C:38](=[CH:39][C:40]3[CH2:41][C:42]([CH3:49])([CH3:48])[CH2:43][C:44]=32)[C:37]1=[O:50])(=[O:27])[CH3:26]

Participants

10

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580438621-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 680968852-Bromo-6-[7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl]benzyl Acetate

Product 1

HCID 68096416HCID 68096416, compoundYield 56.1%

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 1-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 109c (210 mg, 0.64 mmol), 167f (140 mg, 0.3 mmol), 1,2-dimethoxyethane (4 mL) and 1M aqueous sodium carbonate (1 mL). After bubbling N2 for 15 min, Pd(PPh3)4 (18 mg, 0.02 mmol) was added. The mixture was heated in microwave to 130° C. for 25 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 CH2Cl2-60:35:5 CH2Cl2:diethyl ether:methanol to afford a 53% yield (93 mg) of 167g.

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 CH2Cl2-60:35:5 CH2Cl2

Sources & evidence

ORD record
ord-ff964e80d2f94b06beb966f1a32877a3
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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