Sodium Carbonate → 3-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

HRID 44049

반응식

HRID 44049 반응식
Cl[C:2]1[CH:7]=[C:6]([F:8])[N:5]2[N:9]=[C:10]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:11]([C:12]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])=[C:4]2[CH:3]=1.[CH3:30][C:31]1[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][C:32]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[C:17]([O:16][C:15]([N:14]([CH3:22])[C:12]([C:11]1[C:10]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[N:9][N:5]2[C:6]([F:8])=[CH:7][C:2]([C:32]3[CH:33]=[C:34]([CH:38]=[CH:39][C:31]=3[CH3:30])[C:35]([OH:37])=[O:36])=[CH:3][C:4]=12)=[O:13])=[O:21])([CH3:20])([CH3:19])[CH3:18]

참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 160860864-Methyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 59233766Tert-butyl 5-chloro-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

생성물 1

HCID 592338333-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
95 °C

실험 절차

To a degassed mixture containing tert-butyl 5-chloro-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate (0.060 g, 0.14 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.047 g, 0.18 mmol), sodium carbonate (0.043 g, 0.43 mmol), dioxane (1.2 mL) and water (0.24 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.005 g, 0.004 mmol). The mixture was stirred at 95° C. for 18 h. The mixture was cooled to room temperature, filtered to remove solids and adjusted to below pH 4 with 1N aqueous hydrochloric acid (2.0 mL). Water was added (10 mL) and the aqueous portion was extracted with ethyl acetate (2×15 mL). The combined organic portions were washed with brine (20 mL) and dried over magnesium sulfate. The mixture was filtered and concentrated to afford 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid as a residue which was used without further purification. LCMS retention time: 2.725 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3OH/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3OH/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 522 (MH+).

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. customto remove solids
  4. additionWater was added (10 mL)
  5. extractionthe aqueous portion was extracted with ethyl acetate (2×15 mL)
  6. washThe combined organic portions were washed with brine (20 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bc917dbd9f7344bb80f36ae4b95ff91e
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536338B2

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