Hydrochloric Acid → 3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)imidazo[1,2-a]pyridin-6-yl)benzoic acid

HRID 44012

반응식

HRID 44012 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]([NH:20][CH3:21])=[O:19])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.B([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28]([OH:30])=[O:29])(O)O.C([O-])([O-])=O.[Cs+].[Cs+].Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([C:25]4[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=4)[C:28]([OH:30])=[O:29])=[CH:7][N:6]3[C:8]=2[C:18](=[O:19])[NH:20][CH3:21])=[CH:12][CH:13]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 27339573-Carboxyphenylboronic acidHCID 592336946-bromo-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide

생성물 1

HCID 592336813-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)imidazo[1,2-a]pyridin-6-yl)benzoic acid수율 78%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

6-Bromo-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide (150 mg, 0.431 mmol) and 3-boronobenzoic acid (107 mg, 0.646 mmol) were slurried into dioxane (5 mL) and water (1 mL). To the reaction mixture was added Cs2CO3 (211 mg, 0.646 mmol) followed by Pd(PPh3)4 (50 mg, 0.043 mmol). The reaction was sealed and heated at 100° C. overnight. The reaction solution was cooled to rt, filter to remove solids, diluted with water (˜10 mL) and acidified with 1N HCl (aq) (1.5 mL, 1.5 mmol). The white precipitate that formed was collected by filtration, washed with water and dried to yield 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)imidazo[1,2-a]pyridin-6-yl)benzoic acid (174 mg, 0.335 mmol, 78% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 13.15 (br s, 1H), 9.01 (s, 1H), 8.25-8.17 (m, 2H), 8.00 (t, J=7.5 Hz, 2H), 7.87 (d, J=8.7 Hz, 1H), 7.86 (d, J=8.6 Hz, 1H), 7.67 (t, J=7.8 Hz, 1H), 7.65-7.59 (m, 1H), 7.59-7.53 (m, 1H), 7.32 (d, J=8.9 Hz, 2H), 2.82 (d, J=4.0 Hz, 3H). LC-MS retention time 1.18 min; m/z 388 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 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 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

후처리

  1. customThe reaction was sealed
  2. temperatureThe reaction solution was cooled to rt
  3. filtrationfilter
  4. customto remove solids
  5. additiondiluted with water (˜10 mL)
  6. customThe white precipitate that formed
  7. filtrationwas collected by filtration
  8. washwashed with water
  9. customdried

출처 및 근거

ORD 기록
ord-634a50b294ca4c238a71a535f08085e5
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536338B2

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