Potassium Phosphate, Tribasic → (S)-2-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde

HRID 519373

반응식

HRID 519373 반응식
Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N:11]2[CH:23]=[CH:22][N:14]3[C:15]4[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=4[CH:21]=[C:13]3[C:12]2=[O:24])[C:3]=1[CH:4]=[O:5].[CH2:25]([C@H:27]1[CH2:32][N:31]([CH:33]2[CH2:36][O:35][CH2:34]2)[CH2:30][CH2:29][N:28]1[C:37]1[CH:38]=[CH:39][C:40]([NH:43][C:44]2[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48](B3OC(C)(C)C(C)(C)O3)[CH:49]=2)=[N:41][CH:42]=1)[CH3:26].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[CH2:25]([C@H:27]1[CH2:32][N:31]([CH:33]2[CH2:34][O:35][CH2:36]2)[CH2:30][CH2:29][N:28]1[C:37]1[CH:38]=[CH:39][C:40]([NH:43][C:44]2[C:45](=[O:60])[N:46]([CH3:59])[CH:47]=[C:48]([C:2]3[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([N:11]4[CH:23]=[CH:22][N:14]5[C:15]6[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=6[CH:21]=[C:13]5[C:12]4=[O:24])[C:3]=3[CH:4]=[O:5])[CH:49]=2)=[N:41][CH:42]=1)[CH3:26]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86683743(S)-3-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866837562-Bromo-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde

생성물 1

HCID 86683758(S)-2-(5-(5-(2-Ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde수율 43.2%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
80 °C

실험 절차

A round-bottomed flask was charged with 2-bromo-4-fluoro-6-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)benzaldehyde 121f (159 mg, 0.41 mmol), 122a (213 mg, 0.43 mmol), PdCl2(dppf) (29 mg, 0.04 mmol), K3PO4 (182 mg, 0.86 mmol), sodium acetate (71 mg, 0.86 mmol), acetonitrile (15 mL), and water (1.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 80° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 122b as a red solid (120 mg, 43%). MS: [M+H]+ 678.3

후처리

  1. customAfter three cycles of vacuum/argon flush
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was purified by silica-gel column chromatography
  5. washeluting with 1:20 methanol/dichloromethane

출처 및 근거

ORD 기록
ord-3a29fb44aca648fdb71d8b66699586a3
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115152B2

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