Sodium Acetate → (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-[(1-methyl-5-{[methyl(oxetan-3-yl)amino]methyl}-1H-pyrazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}phenyl)methyl Acetate

HRID 1919119ノート

反応式

HRID 1919119 の反応式
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH2:16][N:17]([CH3:22])[CH:18]3[CH2:21][O:20][CH2:19]3)[N:13]([CH3:23])[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][C:32]([F:44])=[CH:31][C:30]=1[N:45]1[CH2:56][CH2:55][C:54]2[C:53]3[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50][C:49]=3[S:48][C:47]=2[C:46]1=[O:59])(=[O:26])[CH3:25].CC([O-])=O.[Na+]>CC#N.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:24]([O:27][CH2:28][C:29]1[C:34]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:15]=[C:14]([CH2:16][N:17]([CH3:22])[CH:18]4[CH2:21][O:20][CH2:19]4)[N:13]([CH3:23])[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:33][C:32]([F:44])=[CH:31][C:30]=1[N:45]1[CH2:56][CH2:55][C:54]2[C:53]3[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50][C:49]=3[S:48][C:47]=2[C:46]1=[O:59])(=[O:26])[CH3:25]

参加物

6

反応物 3

HCID 517045Sodium AcetateHCID 580437865-Bromo-1-methyl-3-(1-methyl-5-((methyl(oxetan-3-yl)amino)methyl)-1H-pyrazol-3-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 Acetate

生成物 1

HCID 58043683(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-[(1-methyl-5-{[methyl(oxetan-3-yl)amino]methyl}-1H-pyrazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}phenyl)methyl Acetate収率 67%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6342Acetonitrile溶媒

反応条件

温度
110 °C

実験手順

A sealed tube was charged with the mixture of 5-bromo-1-methyl-3-(1-methyl-5-((methyl(oxetan-3-yl)amino)methyl)-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 320d (250 mg, 0.65 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 (334 mg, 0.65 mmol), Pd(dppf)Cl2 (55 mg, 0.07 mmol), K3PO4.3H2O(345 mg, 1.3 mmol), and NaOAc (105 mg, 1.3 mmol) in CH3CN (20 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 110° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 30:1 methylene chloride/methanol to afford 322a as a yellow solid (300 mg, 56%). MS: [M+H]+ 689.

後処理

  1. customThe system was evacuated
  2. additionrefilled with N2
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash column chromatography
  7. washeluting with 30:1 methylene chloride/methanol

出典と根拠

ORDレコード
ord-df2cbe957f2a4571888faaf9c8c64eca
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…