Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(1-methyl-5-{[6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naph-thyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl)methyl Acetate

HRID 1919082ノート

反応式

HRID 1919082 の反応式
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[CH2:17][N:16]([CH:21]4[CH2:24][O:23][CH2:22]4)[CH2:15][CH2:14][C:13]=3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:25]([O:28][CH2:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:57][CH2:56][C:55]2[C:54]3[CH2:53][C:52]([CH3:59])([CH3:58])[CH2:51][C:50]=3[S:49][C:48]=2[C:47]1=[O:60])(=[O:27])[CH3:26].CC(O[Na])=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC#N.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]>[C:25]([O:28][CH2:29][C:30]1[C:35]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][N:16]([CH:21]5[CH2:24][O:23][CH2:22]5)[CH2:15][CH2:14][C:13]=4[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:57][CH2:56][C:55]2[C:54]3[CH2:53][C:52]([CH3:59])([CH3:58])[CH2:51][C:50]=3[S:49][C:48]=2[C:47]1=[O:60])(=[O:27])[CH3:26]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 580437985-Bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-oneHCID 67016224(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl AcetateHCID 178418247HCID 178418247、化合物

生成物 1

HCID 68208425(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(1-methyl-5-{[6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naph-thyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl)methyl Acetate収率 57.3%

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
110 °C

実験手順

A 25 mL sealed tube was charged with 5-bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-one 219a (400 mg, 1.0 mmol), (2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 247b (493 mg, 1.0 mmol), CH3COONa (168 mg, 2.0 mmol), K3PO4 (546 mg, 2.0 mmol), PdCl2(dppf) (84 mg, 0.1 mmol) suspended in CH3CN (25 mL) and H2O (1 mL). The mixture was heated at 110° C. for 2 hours. It was then evaporated and the residue was purified by column chromatography eluting with 20:1 methylene chloride/methanol (20:1) to give 280a as a brown solid (400 mg, 56%). MS: (M+H)+ 698.

後処理

  1. customA 25 mL sealed tube
  2. customIt was then evaporated
  3. customthe residue was purified by column chromatography
  4. washeluting with 20:1 methylene chloride/methanol (20:1)

出典と根拠

ORDレコード
ord-654b20dfd2094fa0985af802914abbed
出典データセット
uspto-grants-2013_12
特許番号
US08618107B2

反応ノート

読み込み中…