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

HRID 225440

반응식

HRID 225440 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 18373917Acetonitrile--water (1/1)용매

반응 조건

온도
85 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-73892c8e249c49fb842bd60473a1ce42
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557100B2

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