Potassium Carbonate → (4-Pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid

HRID 474140

반응식

HRID 474140 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)O1.Br[C:21]1[CH:22]=[N:23][N:24]2[C:29]=1[CH:28]=[CH:27][CH:26]=[N:25]2.C(=O)([O-])[O-].[K+].[K+]>CC#N.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[N:23]1[N:24]2[N:25]=[CH:26][CH:27]=[CH:28][C:29]2=[C:21]([C:9]2[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=2)[CH:22]=1

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 37190022-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic AcidHCID 529880243-Bromopyrazolo(1,5-b)pyridazine

생성물 1

HCID 59535942(4-Pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid수율 72%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl촉매HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

To a solution of 1.00 g (3.82 mmol) [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetic acid in 5.70 ml CH3CN and 3.80 ml water was added 0.76 g (3.82 mmol) 3-bromopyrazolo[1,5-b]pyridazine, 8.57 mg (0.038 mmol) palladium acetate, 1.21 g (8.77 mmol) potassium carbonate, and 0.031 g (0.076 mmol) SPhos. The resulting suspension was degassed for 5 minutes. After 30 min in the microwave at 150° C., the reaction mixture was cooled, acidified with 1N HCl, extracted with ethyl acetate, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes) afforded 0.69 g (72%) (4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid. 1H NMR (CD3OD, 400 MHz) 8.40 (dd, J=1.83, 15.75 Hz, 1H); 8.40 (m, 1H); 8.28 (s, 1H); 7.62 (d, J=8.05 Hz, 2H); 7.41 (d, J=7.97 Hz, 2H); 7.22 (dd, J=4.4, 9.1 Hz, 1H); 3.66 (s, 2H). ES-MS M+1=254.1.

후처리

  1. customThe resulting suspension was degassed for 5 minutes
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-2c2f6a5a0b39430b86692d9ef40f1ed5
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637513B2

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