Dimethylformamide → 3-Chloro-4-{8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl}benzoic acid methyl ester

HRID 387217

反応式

HRID 387217 の反応式
Br[C:2]1[C:25](=[O:26])[N:24]([CH2:27][CH3:28])[C:5]2[N:6]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:8]=[CH:9][C:4]=2[CH:3]=1.[Cl:29][C:30]1[CH:35]=[C:34]([C:36]([O:38][CH3:39])=[O:37])[CH:33]=[CH:32][C:31]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O>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].O>[CH3:39][O:38][C:36](=[O:37])[C:34]1[CH:33]=[CH:32][C:31]([C:2]2[C:25](=[O:26])[N:24]([CH2:27][CH3:28])[C:5]3[N:6]=[C:7]([NH:10][C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[N:8]=[CH:9][C:4]=3[CH:3]=2)=[C:30]([Cl:29])[CH:35]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 221712912-Chloro-4-(methoxycarbonyl)benzeneboronic acidHCID 667604546-Bromo-8-ethyl-2-[[4-(4-methylpiperazin-1-yl)phenyl]amino]-8H-pyrido[2,3-d]pyrimidin-7-one

生成物 1

HCID 671196003-Chloro-4-{8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl}benzoic acid methyl ester収率 60%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

実験手順

6-Bromo-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (5, 110 mg, 0.25 mmol), 2-chloro-4-(methoxycarbonyl)benzene boronic acid (58 mg, 0.27 mmol), K3PO4 (58 mg, 0.27 mmol) and PdCl2(dppf) (20 mg, 0.02 mmol) were mixed under argon in a degassed mixture of dimethylformamide and water (20:1, 4.5 mL). The resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor. The reaction mixture was evaporated and the residue was purified by column chromatography, eluting with dichloromethane:methanol (95:5). The title compound (78 mg, 0.15 mmol, 60%) was obtained as a yellow solid. ESMS m/z 533 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.55 (s, 1H) 8.15 (d, J=1.5 Hz, 1H) 7.97 (dd, J=7.9, 1.5 Hz, 1H) 7.51-7.64 (m, 3H) 7.48 (d, J=7.8 Hz, 1H) 7.27 (br. s., 1H) 6.97 (d, J=9.0 Hz, 2H) 4.49 (q, J=7.3 Hz, 2H) 3.95 (s, 3H) 3.18-3.35 (m, 4H) 2.67 (br. s., 4H) 2.42 (br. s., 3H) 1.38 (t, J=7.3 Hz, 3H).

後処理

  1. customThe resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor
  2. customThe reaction mixture was evaporated
  3. customthe residue was purified by column chromatography
  4. washeluting with dichloromethane:methanol (95:5)

出典と根拠

ORDレコード
ord-3758a93220e64d20aed78bcfcf598488
出典データセット
uspto-grants-2013_02
特許番号
US08372970B2

関連ノート

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