Cesium carbonate → HCID 67413047, 화합물

HRID 515224노트

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HRID 515224 반응식
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].Br[C:29]1[N:34]=[C:33]([CH2:35][OH:36])[CH:32]=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[F:27][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:29]3[N:34]=[C:33]([CH2:35][OH:36])[CH:32]=[CH:31][CH:30]=3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:25])=[O:26]

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 3517811(6-Bromopyridin-2-yl)methanolHCID 67413064HCID 67413064, 화합물

생성물 1

HCID 67413047HCID 67413047, 화합물

시약·촉매·용매 4

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (12-1) (131 mg, 0.33 mmol, 1.0 eq), (6-bromopyridin-2-yl)methanol (61 mg, 0.33 mmol, 1.0 eq), cesium carbonate (317 mg, 0.97 mmol, 3.0 eq) and bis(tri-t-butylphosphine) palladium(0) (16.6 mg, 0.03 mmol, 0.1 eq) were combined in dioxane (1.0 mL) and water (0.2 mL). The resulting mixture was heated in the microwave at 120° C. for 20 minutes. The reaction mixture was diluted with EtOAc (10 mL), washed with water (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (12 g SiO2, 0-80% EtOAc in hexanes) to afford (6-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}pyridin-2-yl)methanol (25-1). LRMS m/z (M+H) 382.2 found, 382.1 required.

후처리

  1. washwashed with water (2 mL) and brine (2 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash chromatography (12 g SiO2, 0-80% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-561e41129dc546d481f8a1769dff119e
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108937B2

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