Dichloromethane → 5-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}nicotinonitrile

HRID 1499833ノート

反応式

HRID 1499833 の反応式
Br[C:2]1[C:3]([O:23][CH3:24])=[C:4]([CH:10]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([NH2:21])=[C:15]3[C:14]([CH3:22])=[N:13]2)[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:33]2[CH:34]=[N:35][CH:36]=[C:37]([CH:40]=2)[C:38]#[N:39])O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)C.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[NH2:21][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[N:12]([CH:10]([C:4]3[C:3]([O:23][CH3:24])=[C:2]([C:33]4[CH:34]=[N:35][CH:36]=[C:37]([CH:40]=4)[C:38]#[N:39])[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=3)[CH3:11])[N:13]=[C:14]([CH3:22])[C:15]=12

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 164142165-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrileHCID 866776451-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 866777535-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}nicotinonitrile

試薬・触媒・溶媒 3

HCID 178418228Bis(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
95 °C

実験手順

A mixture of 1-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (first peak from Example 167, step 4 chiral separation, 106 mg, 0.25 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile (70.0 mg, 0.31 mmol, from Combi-Blocks Catalog, item # PN-8893), sodium carbonate (43 mg, 0.41 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (33 mg, 0.041 mmol) in acetonitrile (2 mL)/water (0.6 mL) was degassed with N2 and then stirred at 95° C. for 2 h. The mixture was diluted with methylene chloride, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product (95 mg, 87%) was purified by chromatography eluting with CH2Cl2/MeOH (max. MeOH 5%). LCMS calculated for C22H21ClN7O (M+H)+: m/z=434.2; Found: 434.2.

後処理

  1. customwas degassed with N2
  2. additionThe mixture was diluted with methylene chloride
  3. washwashed with sat. NaHCO3, water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product (95 mg, 87%) was purified by chromatography
  8. washeluting with CH2Cl2/MeOH (max. MeOH 5%)

出典と根拠

ORDレコード
ord-4418e29df68041379b9d8be892edc283
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

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