1,2-Dimethoxyethane → HCID 67016296, compound

HRID 1919105Notes

Reaction equation

HRID 1919105 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH2:17][CH3:18])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:19]([O:22][CH2:23][C:24]1[C:29]([N:30]2[CH2:41][CH2:40][N:39]3[C:32](=[CH:33][C:34]4[CH2:35][C:36]([CH3:43])([CH3:42])[CH2:37][C:38]=43)[C:31]2=[O:44])=[CH:28][C:27]([F:45])=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1)(=[O:21])[CH3:20].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>[CH2:17]([N:13]1[C:14]([CH3:16])=[CH:15][C:11]([NH:10][C:4]2[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=[C:2]([C:25]3[C:24]([CH2:23][O:22][C:19](=[O:21])[CH3:20])=[C:29]([N:30]4[CH2:41][CH2:40][N:39]5[C:32](=[CH:33][C:34]6[CH2:35][C:36]([CH3:42])([CH3:43])[CH2:37][C:38]=65)[C:31]4=[O:44])[CH:28]=[C:27]([F:45])[CH:26]=3)[CH:3]=2)=[N:12]1)[CH3:18]

Participants

10

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580442355-Bromo-3-(1-ethyl-5-methyl-1H-pyrazol-3-ylamino)-1-methylpyridin-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 67016296HCID 67016296, compoundYield 63.3%

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 302a (170 mg, 0.5 mmol), 230a (350 mg, 0.7 mmol), 1,2-dimethoxyethane (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 60% yield (190 mg) of 302b.

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-a26ddb9090564bc6a9f576beb9c433ba
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…