Sulfuric Acid → HCID 86685628, 화합물

HRID 332837

반응식

HRID 332837 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15]C(=O)[O-])[CH:5]=[N:4][C:3]=1[C:19]#[N:20].[F:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([NH2:28])[CH:27]=1.C(=O)([O-])[O-:30].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.OS(O)(=O)=O>O1CCOCC1.C(O)(C(F)(F)F)=O.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:6]1[N:7]=[C:2]([NH:28][C:26]2[CH:25]=[N:24][CH:23]=[C:22]([F:21])[CH:27]=2)[C:3]([C:19]([NH2:20])=[O:30])=[N:4][CH:5]=1

참가 물질

10

반응물 5

HCID 1118Sulfuric AcidHCID 10796Cesium carbonateHCID 5744505-Fluoro-3-pyridinamineHCID 634876Binap, (A+-)-HCID 86685625HCID 86685625, 화합물

생성물 1

HCID 86685628HCID 86685628, 화합물수율 85.8%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6422Trifluoroacetic acid용매HCID 312751,4-Dioxane용매

반응 조건

온도
110 °C

실험 절차

The mixture of tert-tutyl ((1S,2R)-2-((6-chloro-5-cyanopyrazin-2-yl)amino)cyclohexyl)carbamate (100 mg, 0.28 mmol), 3-fluoro-5-aminopyridine (60 mg, 0.56 mmol), powder cesium carbonate (360 mg, 1.12 mmol), BINAP (37 mg, 0.06 mmol), Pd(OAc)2 (14 mg, 0.06 mmol) in 20 mL dioxane was degassed with argon stream. It was stirred in argon atmosphere at 110° C. for 2 h. The mixture was cooled, diluted with 100 mL EtOAc, vigorously stirred, and filtered through celite. The filtrate was concentrated and subjected to silica flash column with 0-60% EtOAc in hexane to isolate the coupling product. It was then stirred in 6 mL TFA and 1 mL conc. H2SO4 at 80° C. for 30 m. It was cooled in ice bath, diluted with water, filtered, and subjected to reverse phase preparative HPLC to isolate the title compound (83 mg). MS found for C16H20FN7O as (M+H)+ 346.5. UV: λ=259, 301 nm. 1H NMR: (CD3OD) δ 9.04 (1H, m), 8.57 (1H, m), 8.40 (1H, m), 7.73 (1H, s), 4.49 (1H, m), 3.74 (1H, m), 1.96-1.60 (8H, m) ppm.

후처리

  1. customwas degassed with argon stream
  2. temperatureThe mixture was cooled
  3. additiondiluted with 100 mL EtOAc
  4. stirringvigorously stirred
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated
  7. customto isolate the coupling product
  8. customat 80° C.
  9. temperatureIt was cooled in ice bath
  10. filtrationfiltered

출처 및 근거

ORD 기록
ord-29df8ee851fc429f83591399850729bf
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877760B2

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