Water → 5-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}-N,N-dimethylpyridine-2-carboxamide

HRID 1499741ノート

反応式

HRID 1499741 の反応式
[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[CH:22]=[C:21]([Cl:23])[C:18]([C:19]#[N:20])=[C:17](Br)[C:16]=3[O:25][CH2:26][CH3:27])[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:28][N:29]([CH3:41])[C:30]([C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)=[O:31].C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].O.ClCCl>>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:13]([C:15]3[C:16]([O:25][CH2:26][CH3:27])=[C:17]([C:35]4[CH:34]=[CH:33][C:32]([C:30]([N:29]([CH3:41])[CH3:28])=[O:31])=[N:37][CH:36]=4)[C:18]([C:19]#[N:20])=[C:21]([Cl:23])[CH:22]=3)[CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1

参加物

7

反応物 6

HCID 962WaterHCID 6342AcetonitrileHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 53438177[6-(Dimethylcarbamoyl)pyridin-3-yl]boronic acidHCID 866776704-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile

生成物 1

HCID 866776715-{3-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-6-cyano-2-ethoxyphenyl}-N,N-dimethylpyridine-2-carboxamide収率 24.1%

反応条件

温度
100 °C

実験手順

To a mixture of 4-[1-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile (20 mg, 0.04 mmol) and {6-[(dimethylamino)carbonyl]pyridin-3-yl}boronic acid (13 mg, 0.069 mmol) in acetonitrile (2 mL, 40 mmol) was added sodium carbonate (10 mg, 0.09 mmol) in water (0.5 mL, 30 mmol). The reaction was degassed with bubbling nitrogen. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2 mg, 0.002 mmol) was added and degassed more with N2. Reaction was heated at 100° C. for 1 h. The crude product was purified on preparative LC-MS (acetonitrile, water, TFA) to give the desired product (0.005 g, 20%) as white amorphous solid. The product was isolated as a racemic mixture. LCMS calculated for C26H24ClN7O3(M+H)+: m/z=518.1; found: 518.1.

後処理

  1. customThe reaction was degassed with bubbling nitrogen
  2. customdegassed more with N2
  3. customReaction
  4. customThe crude product was purified on preparative LC-MS (acetonitrile, water, TFA)

出典と根拠

ORDレコード
ord-2a4bcf0b26e14c6694568f96841e03de
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

読み込み中…