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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
ノート
印刷プレビュー

反応式

HRID 1024097 の反応式
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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 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

生成物 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
収率 39.2%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-99cd002b6da540128b31d2c948190a3d
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08722676B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート