1,2-Dimethoxyethane → HCID 67016178, compound

HRID 1918810Notes

Reaction equation

HRID 1918810 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH:13][C:14]3[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=[C:18](Br)[CH:19]=3)[CH:12]=[C:6]2[CH2:5]1)(=[O:3])[CH3:2].[C:23]([O:26][CH2:27][C:28]1[C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=[CH:30][C:29]=1[N:43]1[CH2:55][CH2:54][N:46]2[C:47]3[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=3[CH:53]=[C:45]2[C:44]1=[O:56])(=[O:25])[CH3:24].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.CCOCC.O.C(OCC)(=O)C>[C:23]([O:26][CH2:27][C:28]1[C:29]([N:43]2[CH2:55][CH2:54][N:46]3[C:47]4[CH2:48][CH2:49][CH2:50][CH2:51][C:52]=4[CH:53]=[C:45]3[C:44]2=[O:56])=[CH:30][CH:31]=[CH:32][C:33]=1[C:18]1[CH:19]=[C:14]([NH:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8][N:7]3[N:10]=2)[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=1)(=[O:25])[CH3:24]

Participants

10

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580438772-(2-(Acetoxymethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneHCID 580440563-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 67016178HCID 67016178, compoundYield 36.9%

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 3-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one 108d (120 mg, 0.3 mmol), 2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 114a (200 mg, 0.4 mmol), DME (4 mL) and 1M aqueous sodium carbonate (1 mL). After bubbling nitrogen for 15 min, Pd(PPh3)4 (19 mg, 0.02 mmol) was added. The mixture was heated in a 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 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 CH2Cl2-60:35:5 CH2Cl2:Et2O:MeOH to afford a 33% yield (69 mg) of 2-(5-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate 108e.

Workup

  1. customA microwave tube equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen 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 CH2Cl2-60:35:5 CH2Cl2

Sources & evidence

ORD record
ord-24f3229d811f4659a9318bc2a87b93fc
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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