Potassium Phosphate, Tribasic → 2-{10-Fluoro-1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrido[3,4-b]indolizin-2-yl}-4-[1-methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde

HRID 592953노트

반응식

HRID 592953 반응식
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH2:22][CH2:21][C:20]3[N:19]4[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)=[C:13]([F:23])[C:12]=3[C:11]2=[O:24])[N:5]=[CH:4][CH:3]=1.[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH:54]4[CH2:57][O:56][CH2:55]4)[CH2:50][C@@H:49]3[CH3:58])=[CH:44][N:43]=2)[C:27]1=[O:59].C([O-])(=O)C.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.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].C(#N)C>[F:23][C:13]1[C:12]2[C:11](=[O:24])[N:10]([C:6]3[C:7]([CH:8]=[O:9])=[C:2]([C:30]4[CH:29]=[C:28]([NH:41][C:42]5[CH:47]=[CH:46][C:45]([N:48]6[CH2:53][CH2:52][N:51]([CH:54]7[CH2:55][O:56][CH2:57]7)[CH2:50][C@@H:49]6[CH3:58])=[CH:44][N:43]=5)[C:27](=[O:59])[N:26]([CH3:25])[CH:31]=4)[CH:3]=[CH:4][N:5]=3)[CH2:22][CH2:21][C:20]=2[N:19]2[C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18]2

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 866844464-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

생성물 1

HCID 866844452-{10-Fluoro-1-oxo-1H,2H,3H,4H,6H,7H,8H,9H-pyrido[3,4-b]indolizin-2-yl}-4-[1-methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]pyridine-3-carbaldehyde수율 214.5%

시약·촉매·용매 3

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

반응 조건

온도
95 °C

실험 절차

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 134c (70 mg, 0.20 mmol), 1-methyl-3-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2-one 191j (192 mg, 0.40 mmol), Pd(dppf)Cl2 (33 mg, 0.040 mmol), potassium acetate (39 mg, 0.40 mmol), K3PO4 (87 mg, 0.40 mmol), acetonitrile (7 mL), and water (6 drops). After three cycles of vacuum/argon flush, the mixture was heated at 95° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 50:1 ethyl acetate/methanol to afford 237a (286 mg, purity: 46%, yield: 98%) as a solid. MS-ESI: [M+H]+ 667.3

후처리

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 50:1 ethyl acetate/methanol

출처 및 근거

ORD 기록
ord-25ab4392fc064a04bafe59127ca40fc0
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

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