proline dl-form → HCID 59540845, compound

HRID 1677551Notes

Reaction equation

HRID 1677551 reaction equation
I[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]([C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:23]1[C:26]2([CH2:29][NH:28][CH2:27]2)[CH2:25][O:24]1.C(=O)([O-])[O-].[K+].[K+].N1CCCC1C(O)=O>[Cu](I)I>[CH3:19][C:18]([CH3:21])([CH3:20])[C:17]([C:16]1[C:10]2[C:11](=[N:12][CH:13]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([N:28]4[CH2:29][C:26]5([CH2:23][O:24][CH2:25]5)[CH2:27]4)[CH:3]=3)[N:9]=2)[NH:14][CH:15]=1)=[O:22]

Participants

6

Reactant 4

HCID 614proline dl-formHCID 11430Potassium CarbonateHCID 231118872-Oxa-6-azaspiro[3.3]heptaneHCID 59540678HCID 59540678, compound

Product 1

HCID 59540845HCID 59540845, compoundYield 25.1%

Reagents, catalysts & solvents 1

HCID 83717Copper iodideCatalyst

Conditions

Temperature
100 °C

Procedure

1-[2-(3-Iodo-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2,-dimethyl-propan-1-one (150 mg, 0.37 mmol), the oxalate salt of 2-oxa-6-aza-spiro[3.3]heptane (267 mg, 0.93 mmol), potassium carbonate (255 mg, 1.85 mmol), copper iodide (14 mg, 0.074 mmol), and d,l-proline (17 mg, 0.148 mmol) were added to a microwave vial. The vial was capped and purged with nitrogen. DMSO (3.7 ml) was added and the vial was purged with nitrogen again. The reaction was heated in a sand bath at 100° C. for 72 hours. The reaction was poured into ice water, extracted into ethyl acetate, washed with water and brine, dried with sodium sulfate and concentrated. The crude product was purified by flash chromatography using a gradient of 30% to 50% ethyl acetate in hexanes to yield 35 mg (25%) of 2,2-dimethyl-1-{2-[3-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-propan-1-one as a yellow solid. (M+H)+=377; MP=260.0-262.0° C.

Workup

  1. customThe vial was capped
  2. custompurged with nitrogen
  3. additionDMSO (3.7 ml) was added
  4. customthe vial was purged with nitrogen again
  5. additionThe reaction was poured into ice water
  6. extractionextracted into ethyl acetate
  7. washwashed with water and brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-70ef13383cff4475adfab8e42640816e
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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