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

HRID 2079298노트

반응식

HRID 2079298 반응식
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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 11186Zinc cyanide (Zn(CN)2)촉매

반응 조건

온도
200 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-fd321e33b4ab4bd9b32f0f718d524260
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928107B2

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