Dimethylformamide → 4-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrile

HRID 2079298ノート

反応式

HRID 2079298 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[N:19]1[CH2:24][CH2:23][N:22]([C:25](=[O:32])[C@H:26]([OH:31])[CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:20]1.CCOC(C)=O.[CH3:39][N:40](C=O)C>[C-]#N.[C-]#N.[Zn+2]>[OH:31][C@H:26]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:25]([N:22]1[CH2:21][CH2:20][N:19]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:39]#[N:40])[CH:3]=3)[N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:6]=2)[CH2:24][CH2:23]1)=[O:32]

参加物

5

反応物 3

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 136121577(R)-1-(4-(6-bromo-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one

生成物 1

HCID 1361215804-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrile収率 75%

試薬・触媒・溶媒 1

HCID 11186Zinc cyanide (Zn(CN)2)触媒

反応条件

温度
200 °C

実験手順

(R)-1-(4-(6-Bromo-2-(2-hydroxyphenyl)quinazolin-4-yl)piperazin-1-yl)-2-hydroxy-4-methylpentan-1-one (188 mg, 0.38 mmol), Zn(CN)2 (44 mg, 0.38 mmol), and Pd(Ph3)4 (6.5 mg, 0.0112 mmol) were dissolved in DMF (4 mL) and the reaction mixture was heated in a microwave synthesizer at 200° C. for 15 minutes. EtOAc (50 mL) was added and the mixture was washed twice with H2O. The organic layer was dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-40% EtOAc in CH2Cl2:hexanes (1:1) gave 4-[4-((R)-2-hydroxy-4-methyl-pentanoyl)-piperazin-1-yl]-2-(2-hydroxy-phenyl)-quinazoline-6-carbonitrile (127 mg, 75%). LC/MS: m/z 446 (M+H)+ at 3.24 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.60 (d, J=1.5 Hz, 1H), 8.46 (dd, J=8.4, 1.8 Hz, 1H), 8.15 (dd, J=8.7, 1.7 Hz, 1H), 8.00 (d, J=8.7 Hz, 1H), 7.45-7.41 (m, 1H), 6.99-6.95 (m, 2H), 4.94 (d, J=7.0 Hz, 1H), 4.39-4.36 (m, 1H), 4.14-4.04 (m, 4H), 3.89-3.67 (m, 4H), 1.82-1.76 (m, 1H), 1.47-1.37 (m, 2H), 0.93-0.91 (m, 6H) ppm.

後処理

  1. washthe mixture was washed twice with H2O
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification via silica gel chromatography

出典と根拠

ORDレコード
ord-fd321e33b4ab4bd9b32f0f718d524260
出典データセット
uspto-grants-2011_04
特許番号
US07928107B2

反応ノート

読み込み中…