Cesium carbonate → Tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate

HRID 63363

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HRID 63363 반응식
Cl[C:2]1[CH:7]=[C:6]([CH2:8][O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:34][C:35]1[CH:40]=[N:39][CH:38]=[C:37]([CH2:41][CH3:42])[N:36]=1.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>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:41]([C:37]1[N:36]=[C:35]([NH:34][C:2]2[CH:7]=[C:6]([CH2:8][O:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[CH:12][CH:11]=3)[CH:5]=[CH:4][N:3]=2)[CH:40]=[N:39][CH:38]=1)[CH3:42]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 457882966-Ethylpyrazin-2-amineHCID 118317288Tert-butyl (4-((2-chloropyridin-4-yl)methoxy)naphthalen-1-yl)carbamate2회

생성물 1

HCID 118317293Tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate수율 76.9%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
20 °C

실험 절차

Dioxane (125 mL) was added to tert-butyl (4-((2-chloropyridin-4-yl)methoxy)naphthalen-1-yl)carbamate (Intermediate C) (9.6 g) and the mixture stirred at 20° C. Cesium carbonate (2 eq, 16.3 g) and 2-amino-6-ethylpyrazine (1.5 eq, 4.8 g) were added to the stirred mixture at ° C. Argon was purged through the reaction mixture. Tris(dibenzylideneacetone)dipalladium(0) (0.05 eq, 1.14 g) and racemic BINAP (0.10 eq, 1.56 g) were added to the reaction mixture. The mixture was stirred for an additional 15 min at 20° C. The mixture was heated to 90° C. at a rate of 1.5 K/min then stirred for 12 h at 90° C. The mixture was cooled to 20° C. and stirring continued for an additional 6 h. The heterogeneous mixture was filtered over Celite, and the filter washed with dioxane (twice 5 mL). The filtrate was concentrated in vacuo at 20 mbar and 50° C. The residue was dissolved in ethanol (150 mL). Spontaneous crystallization occurred. The heterogeneous mixture was stirred for 3 h at 22° C. The precipitate was filtered and washed with ethanol (10 mL). The product was dried in vacuo at 50° C. for 20 h to give tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate (9.05 g, 76.8%).

후처리

  1. customArgon was purged through the reaction mixture
  2. stirringThe mixture was stirred for an additional 15 min at 20° C
  3. temperatureThe mixture was heated to 90° C. at a rate of 1.5 K/min
  4. stirringthen stirred for 12 h at 90° C
  5. temperatureThe mixture was cooled to 20° C.
  6. stirringstirring
  7. filtrationThe heterogeneous mixture was filtered over Celite
  8. washthe filter washed with dioxane (twice 5 mL)
  9. concentrationThe filtrate was concentrated in vacuo at 20 mbar and 50° C
  10. dissolutionThe residue was dissolved in ethanol (150 mL)
  11. customSpontaneous crystallization
  12. stirringThe heterogeneous mixture was stirred for 3 h at 22° C
  13. filtrationThe precipitate was filtered
  14. washwashed with ethanol (10 mL)
  15. customThe product was dried in vacuo at 50° C. for 20 h

출처 및 근거

ORD 기록
ord-b06270fffe6b44dc8a0a60b274ccb442
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447076B2

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