Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{5-[(5-{[(3R,5S)-3,5-dimethylmorpholin-4-yl]carbonyl}pyridin-2-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate

HRID 1022208ノート

反応式

HRID 1022208 の反応式
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1B1OC(C)(C)C(C)(C)O1)(=[O:29])[CH3:28].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>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.C(#N)C>[C:27]([O:30][CH2:31][C:32]1[C:33]([N:47]2[CH2:58][CH2:57][N:56]3[C:49](=[CH:50][C:51]4[CH2:52][C:53]([CH3:60])([CH3:59])[CH2:54][C:55]=43)[C:48]2=[O:61])=[N:34][CH:35]=[CH:36][C:37]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([N:19]3[C@@H:24]([CH3:25])[CH2:23][O:22][CH2:21][C@H:20]3[CH3:26])=[O:18])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:29])[CH3:28]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86684419(2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetateHCID 866845715-Bromo-3-(5-((3R,5S)-3,5-dimethylmorpholine-4-carbonyl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

生成物 1

HCID 86684572(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-{5-[(5-{[(3R,5S)-3,5-dimethylmorpholin-4-yl]carbonyl}pyridin-2-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl Acetate収率 64.5%

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
90 °C

実験手順

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 320b (150 mg, 1.0 eq., 0.36 mmol), {3-[(acetoxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (286 mg, 2.0 eq., 0.72 mmol), PdCl2(dppf) (29 mg, 0.10 eq., 0.040 mmol), K3PO4 (153 mg, 2.0 eq., 0.72 mmol), sodium acetate (59 mg, 2.0 eq., 0.72 mmol), acetonitrile (10 mL), and water (0.2 mL). After three cycles of vacuum/nitrogen flush, the mixture was heated at 90° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 320c (161 mg, 64%) as brown solid. MS-ESI: [M+H]+ 693.8

後処理

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/nitrogen flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-0118ef692894410fba3dedb324ee9fc5
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

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