Sodium Carbonate → HCID 71276087, 화합물

HRID 518253

반응식

HRID 518253 반응식
NC1N=C(N[C@H]([C:11]2[N:12](C3C=CC=CC=3)[C:13](=[O:22])[C:14]3[C:19]([CH:20]=2)=CC=CC=3Cl)C)C(C#N)=CN=1.[NH2:31][C:32]1[N:37]=[C:36]([NH:38][C@H:39]([C:41]2[N:42]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:43](=[O:52])[C:44]3[C:49]([CH:50]=2)=[CH:48][CH:47]=[CH:46][C:45]=3Cl)[CH3:40])[C:35]([C:59]([O:61][CH2:62][CH3:63])=[O:60])=[CH:34][N:33]=1.B(O)O.[CH:67]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:31][C:32]1[N:37]=[C:36]([NH:38][C@H:39]([C:41]2[N:42]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:43](=[O:52])[C:44]3[C:49]([CH:50]=2)=[CH:48][CH:47]=[CH:46][C:45]=3[C:19]2[CH:20]=[CH:11][N:12]=[C:13]([O:22][CH3:67])[CH:14]=2)[CH3:40])[C:35]([C:59]([O:61][CH2:62][CH3:63])=[O:60])=[CH:34][N:33]=1

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 67950671(S)-2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrileHCID 71275988HCID 71275988, 화합물

생성물 1

HCID 71276087HCID 71276087, 화합물

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
120 °C

실험 절차

Compound 109 was prepared from compound 8 according to Method G. Compound 109 was then converted to compound 110 according to the following procedure: The mixture of (S)-ethyl 2-amino-4-((1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate (300 mg, 0.65 mmol) and 2-methoxypyridin-4-yl)boronic acid (149 mg, 0.98 mmol) in 1,4-dioxane:water (3:1, 12 mL) was degassed and backfilled with argon (three cycles). To this mixture, 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (121 mg, 0.26 mmol), palladium(II) acetate (29 mg, 0.13 mmol), and Na2CO3 (207 mg, 1.95 mmol) were added sequentially. The resulting mixture was degassed and backfilled with argon (three cycles), and then stirred at 120° C. for 3 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM) to afford the product 110, (S)—ethyl 2-amino-4-((1-(8-(2-methoxypyridin-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxylate.

후처리

  1. customwas degassed
  2. customThe resulting mixture was degassed
  3. temperatureto cool to RT
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-46eca5275bda46f99b7b708a2963f50f
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115141B2

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