Potassium Phosphate, Tribasic → 4-Fluoro-2-(6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenylamino)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-2-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl Acetate

HRID 1024092노트

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HRID 1024092 반응식
[C:1]([O:4][CH2:5][C:6]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][C:9]([F:21])=[CH:8][C:7]=1[N:22]1[CH2:34][CH2:33][C:32]2[N:31]3[C:26]([CH2:27][CH2:28][CH2:29][CH2:30]3)=[CH:25][C:24]=2[C:23]1=[O:35])(=[O:3])[CH3:2].I[C:37]1[N:45]=[C:44]2[C:40]([N:41]=[CH:42][N:43]2[CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])=[C:39]([NH:54][C:55]2[CH:60]=[CH:59][C:58]([N:61]3[CH2:66][CH2:65][N:64]([CH:67]4[CH2:70][O:69][CH2:68]4)[CH2:63][CH2:62]3)=[CH:57][CH:56]=2)[N:38]=1.[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>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:22]2[CH2:34][CH2:33][C:32]3[N:31]4[C:26]([CH2:27][CH2:28][CH2:29][CH2:30]4)=[CH:25][C:24]=3[C:23]2=[O:35])=[CH:8][C:9]([F:21])=[CH:10][C:11]=1[C:37]1[N:45]=[C:44]2[C:40]([N:41]=[CH:42][N:43]2[CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:51])([CH3:52])[CH3:53])=[C:39]([NH:54][C:55]2[CH:56]=[CH:57][C:58]([N:61]3[CH2:66][CH2:65][N:64]([CH:67]4[CH2:68][O:69][CH2:70]4)[CH2:63][CH2:62]3)=[CH:59][CH:60]=2)[N:38]=1)(=[O:3])[CH3:2]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866841532-Iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amineHCID 866841614-Fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

생성물 1

HCID 866841604-Fluoro-2-(6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenylamino)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-2-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl Acetate수율 67.1%

시약·촉매·용매 3

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

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온도
100 °C

실험 절차

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 120f (400 mg, 0.82 mmol), 2-iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amine 117f (604 mg, 0.99 mmol), PdCl2(dppf) (33 mg, 0.040 mmol), K3PO4 (347 mg, 1.64 mmol), and sodium acetate (134 mg, 1.64 mmol), acetonitrile (15 mL), and water (1 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 120g (460 mg, 66%) as a green solid. MS-ESI: [M+H]+ 836.4.

후처리

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-fa199e2702b845e5aee46718d831107d
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722676B2

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