Sodium Carbonate → 2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-pyrazin-2-yl-benzaldehyde

HRID 225440

Reaction equation

HRID 225440 reaction equation
[CH3:1][CH:2]1[O:7][CH:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:16]([F:17])=[C:15]([F:18])[C:14](B3OC(C)(C)C(C)(C)O3)=[CH:13][C:10]=2[CH:11]=[O:12])[CH2:3]1.I[C:29]1[CH:34]=[N:33][CH:32]=[CH:31][N:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC#N.O>[CH3:8][CH:6]1[O:7][CH:2]([CH3:1])[CH2:3][N:4]([C:9]2[C:16]([F:17])=[C:15]([F:18])[C:14]([C:29]3[CH:34]=[N:33][CH:32]=[CH:31][N:30]=3)=[CH:13][C:10]=2[CH:11]=[O:12])[CH2:5]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 642841IodopyrazineHCID 760452232-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde

Product 1

HCID 866144992-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-pyrazin-2-yl-benzaldehydeYield 68%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (16 grams, 41 mmol), 2-iodopyrazine (Aldrich, 6 grams, 29.1 mmol), sodium carbonate (9.3 grams, 87 mmol) and Pd(PPh3)2Cl2 (Aldrich, 0.82 gram, 1.2 mmol) were suspended in a 1:1 mixture of CH3CN/H2O. The reaction mixture was then purged with nitrogen and heated at 85° C. overnight. Upon completion the reaction was partitioned between H2O and ethyl acetate and the aqueous layer was extracted twice with ethyl acetate. The combined extracts were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography eluting with 5-40% ethyl acetate in hexanes to obtain 6.6 grams of the desired product. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (d, J=6.2 Hz, 6H), 3.09 (m, 4H), 3.84 (m, 1H), 8.28 (dd, J=8.1, 2.1 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.66 (dd, J=2.4, 1.7 Hz, 1H), 9.01 (s, 1 H), 10.22 (s, 1H); MS(APCl+) m/z 334 (MH+).

Workup

  1. customThe reaction mixture was then purged with nitrogen
  2. customUpon completion the reaction was partitioned between H2O and ethyl acetate
  3. extractionthe aqueous layer was extracted twice with ethyl acetate
  4. dry with materialThe combined extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography
  8. washeluting with 5-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-73892c8e249c49fb842bd60473a1ce42
Source dataset
uspto-grants-2009_07
Patent number
US07557100B2

Linked notes

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