Potassium Phosphate, Tribasic → 1-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

HRID 710936

반응식

HRID 710936 반응식
Br[C:2]1[N:7]2[N:8]=[C:9]([C:11]3([C:14]([OH:16])=[O:15])[CH2:13][CH2:12]3)[N:10]=[C:6]2[C:5]([O:17][CH3:18])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][CH:35]=2)[C:32](=[O:36])[O:31][CH2:30]3)O1.B([O-])[O-].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:18][O:17][C:5]1[C:6]2[N:7]([N:8]=[C:9]([C:11]3([C:14]([OH:16])=[O:15])[CH2:13][CH2:12]3)[N:10]=2)[C:2]([C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][CH:35]=2)[C:32](=[O:36])[O:31][CH2:30]3)=[CH:3][CH:4]=1

참가 물질

10

반응물 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 867645081-(5-Bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropane-1-carboxylic acidHCID 178514824HCID 178514824, 화합물

생성물 1

HCID 686549441-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

1-(5-Bromo-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxylic acid (1.00 g, 3.20 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-isobenzofuran-1-one (preparation of the boronate was described in WO2011/134468) (1.67 g, 6.40 mmol) were dissolved in degassed dioxane (16 mL). Pd2(dba)3 (29 mg, 32 μmol), PCy3 (18 mg, 64 μmol) and K3PO4 (2.38 g, 11.2 mmol) were mixed in degassed water (10 mL). The two solutions were mixed and subsequently heated in a micro wave oven to 110° C. for 10 minutes, cooled to room temperature and diluted with EtOAc (40 mL). The organic phase was extracted with water (25 mL) and an aqueous 0.1 M solution of NaOH (25 mL) and the combined aqueous phases were acidified with conc. HCl to pH 0-1, and extracted with DCM (30 mL×4). Upon evaporation of the combined organic phases the title compound crystallized out (746 mg, 64%). HPLC-Retention time (XE Metode 7 CM): 1.97 minutes. Detected “M+1”-mass: 366.11. Calculated “M+1”-mass: 366.11. 1H NMR (DMSO, 300 MHz): δ=8.25-8.20 (m, 1H), 8.13 (dd, 1H, J=8.2, 1.4 Hz), 8.00 (d, 1H, J=8.0 Hz), 7.40 (d, 1H, J=8.2 Hz), 7.24 (d, 1H, J=8.3 Hz), 5.51 (s, 2H), 4.04 (s, 3H), 1.58-1.48 (m, 2H), 1.48-1.39 (m, 2H) ppm.

후처리

  1. additionThe two solutions were mixed
  2. temperaturecooled to room temperature
  3. extractionThe organic phase was extracted with water (25 mL)
  4. extractionextracted with DCM (30 mL×4)
  5. customUpon evaporation of the combined organic phases the title compound
  6. customcrystallized out (746 mg, 64%)
  7. custom1.97 minutes

출처 및 근거

ORD 기록
ord-afa63f2269334d41a114e04bb9857661
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181248B2

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