1,2-Dimethoxyethane → HCID 58043715, compound

HRID 1919043Notes

Reaction equation

HRID 1919043 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[C:14]3[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:21]([O:24][CH2:25][C:26]1[C:31]([N:32]2[CH2:43][CH2:42][N:41]3[C:34](=[CH:35][C:36]4[CH2:37][C:38]([CH3:45])([CH3:44])[CH2:39][C:40]=43)[C:33]2=[O:46])=[CH:30][C:29]([F:47])=[CH:28][C:27]=1B1OC(C)(C)C(C)(C)O1)(=[O:23])[CH3:22].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.O.C(OCC)(=O)C>[F:47][C:29]1[CH:28]=[C:27]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:20]=[C:14]4[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][N:13]4[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[C:26]([CH2:25][O:24][C:21](=[O:23])[CH3:22])=[C:31]([N:32]2[CH2:43][CH2:42][N:41]3[C:34](=[CH:35][C:36]4[CH2:37][C:38]([CH3:44])([CH3:45])[CH2:39][C:40]=43)[C:33]2=[O:46])[CH:30]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580438845-Bromo-1-methyl-3-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-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 58043715HCID 58043715, compoundYield 37.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

A microwave tube equipped with a magnetic stirrer was charged with 5-bromo-1-methyl-3-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one 146a (210 mg, 0.6 mmol), 230a (460 mg, 0.9 mmol), 1,2-dimethoxyethane (8 mL) and 1M aqueous sodium carbonate (2 mL). After bubbling N2 for 15 min, Pd(PPh3)4 (36 mg, 0.03 mmol) was added. The mixture was heated in microwave to 135° 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 37% yield (140 mg) of 246a.

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/diethyl ether/methanol

Sources & evidence

ORD record
ord-f4f59e7831074de7bcd06d2bff6496c8
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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