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 1429871

反応式

HRID 1429871 の反応式
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

参加物

10

反応物 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、化合物

生成物 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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f7cb7d453af147699df991ed14e4fd92
出典データセット
uspto-grants-2015_01
特許番号
US08940761B2

関連ノート

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