Dichloromethane → tert-butyl 4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1972906노트

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HRID 1972906 반응식
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19](Br)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH:41]=2)O1.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([C:36]3[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH:37]=3)[N:20]2[N:21]=[CH:22][N:23]=1

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 585299415-(2-benzyl-2H-indazol-6-yl)-7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine

생성물 1

HCID 58529584tert-butyl 4-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3,6-dihydropyridine-1(2H)-carboxylate수율 69%

시약·촉매·용매 3

HCID 24290Palladium Chloride촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 80711,2-Dimethoxyethane용매

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온도
75 °C

실험 절차

To a stirred suspension of 5-(2-benzyl-2H-indazol-6-yl)-7-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (660 mg, 1.57 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (see Eastwood, P. R. Tetrahedron Lett 2000, 41, 3705 for preparation) (730 mg, 2.36 mmol), and 1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II)-complex with dichloromethane (115 mg, 0.16 mmol) in degassed DME (12 mL) was added aqueous Na2CO3 solution (2 M, 2.4 mL). The reaction was heated (75° C.) for 17 h and was then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL). The layers were separated and the organic layer was washed with brine, dried (Na2SO4), and concentrated to dryness. The crude residue was purified by ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 564 mg (69%) of the desired product, which was approximately 50% pure. ES-MS m/z 522.12 [M+H]+, HPLC RT (min) 3.20.

후처리

  1. temperaturewas then cooled to rt
  2. customThe mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to dryness
  7. customThe crude residue was purified by ISCO® chromatography

출처 및 근거

ORD 기록
ord-5a3cac6980524e6f903ba6dc09806564
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431695B2

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