Pivalic acid → (R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

HRID 81086

반응식

HRID 81086 반응식
C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.C(O)(=O)C(C)(C)C.[F-].[Cs+].Br[C:36]1[CH:41]=[C:40]([CH:42]([CH3:44])[CH3:43])[CH:39]=[CH:38][N:37]=1.[CH:45]1([C@H:49]([NH:51][C:52]2[C:57]3[N:58]([CH2:61][C:62]4[CH:67]=[CH:66][C:65]([C:68]([F:71])([F:70])[F:69])=[CH:64][CH:63]=4)[CH:59]=[N:60][C:56]=3[C:55]([CH3:72])=[C:54]([C:73]#[N:74])[N:53]=2)[CH3:50])[CH2:48][CH2:47][CH2:46]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:45]1([C@H:49]([NH:51][C:52]2[C:57]3[N:58]([CH2:61][C:62]4[CH:63]=[CH:64][C:65]([C:68]([F:71])([F:70])[F:69])=[CH:66][CH:67]=4)[C:59]([C:36]4[CH:41]=[C:40]([CH:42]([CH3:44])[CH3:43])[CH:39]=[CH:38][N:37]=4)=[N:60][C:56]=3[C:55]([CH3:72])=[C:54]([C:73]#[N:74])[N:53]=2)[CH3:50])[CH2:48][CH2:47][CH2:46]1

참가 물질

8

반응물 5

HCID 6417Pivalic acidHCID 25953Cesium fluorideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 457879862-Bromo-4-isopropylpyridineHCID 86724464(R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

생성물 1

HCID 86724465(R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매2회

반응 조건

온도
70 °C

실험 절차

To a vial containing palladium(II) acetate (4.3 mg, 0.019 mmol) and butyldi-1-adamantylphosphine (13.9 mg, 0.039 mmol) was added 1,4-dioxane (300 ul). The vial was evacuated and refilled with Ar (3×). The solution was warmed to 70° C. for 20 minutes. In a separate vial were combined pivalic acid (9.9 mg, 0.097 mmol), cesium fluoride (44 mg, 0.29 mmol), 2-bromo-4-isopropylpyridine (purchased from CombiPhos Catalysts, Inc.) (29 mg, 0.15 mmol), (R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (40 mg, 0.097 mmol) and 1,4-dioxane (0.5 mL). The mixture was degassed with Ar for 15 minutes, and the catalyst solution was added to the mixture. The resulting mixture was stirred at 130° C. for 3 days. The mixture was cooled to room temperature and concentrated. The residue was dissolved in DCM and purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to give (R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C30H31F3N6 [M+H]+ 533. found 533.

후처리

  1. customThe vial was evacuated
  2. additionrefilled with Ar (3×)
  3. customThe mixture was degassed with Ar for 15 minutes
  4. additionthe catalyst solution was added to the mixture
  5. temperatureThe mixture was cooled to room temperature
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DCM
  8. custompurified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

출처 및 근거

ORD 기록
ord-25ba329731bc4cecab261f438551a9a2
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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