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Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-fluoro-6-[6-({4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl}amino)-9-{[2-(trimethylsilyl)ethoxy]methyl}purin-2-yl]phenyl)methyl Acetate

HRID 1024097
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HRID 1024097 반응식
I[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([CH:32]4[CH2:35][O:34][CH2:33]4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[N:3]=1.[C:36]([O:39][CH2:40][C:41]1[C:46]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[CH:45][C:44]([F:62])=[CH:43][C:42]=1B1OC(C)(C)C(C)(C)O1)(=[O:38])[CH3:37].[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].C(#N)C.O>[C:36]([O:39][CH2:40][C:41]1[C:42]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:4]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH:32]5[CH2:35][O:34][CH2:33]5)[CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[N:3]=2)=[CH:43][C:44]([F:62])=[CH:45][C:46]=1[N:47]1[CH2:58][CH2:57][N:56]2[C:49](=[CH:50][C:51]3[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=32)[C:48]1=[O:61])(=[O:38])[CH3:37]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 670162322-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 866841532-Iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amine

생성물 1

HCID 86684163
(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-fluoro-6-[6-({4-[4-(oxetan-3-yl)piperazin-1-yl]phenyl}amino)-9-{[2-(trimethylsilyl)ethoxy]methyl}purin-2-yl]phenyl)methyl Acetate
수율 39.2%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 2-iodo-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-purin-6-amine 117f (360 mg, 0.60 mmol), {2-[(acetyloxy)methyl]-3-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-5-fluorophenyl}boronic acid 110g (360 mg, 0.90 mmol), Pd(dppf)Cl2 (30 mg, 0.030 mmol), K3PO4 (270 mg, 1.2 mmol), sodium acetate (180 mg, 1.2 mmol), water (0.5 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the 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 20:1 dichloromethane/methanol to afford 123a as a yellow solid (200 mg, 35%). MS-ESI: [M+H]+ 850.4

후처리

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 20:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-99cd002b6da540128b31d2c948190a3d
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08722676B2

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