Potassium Phosphate, Tribasic → 4-[1-Methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-{6-oxo-8-thia-4,5-diaza-tricyclo[7.4.0.02,7]tri-deca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde

HRID 592805ノート

反応式

HRID 592805 の反応式
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH:30]4[CH2:33][O:32][CH2:31]4)[CH2:26][C@@H:25]3[CH3:34])=[CH:20][N:19]=2)[C:3]1=[O:35].Cl[C:37]1[CH:42]=[CH:41][N:40]=[C:39]([N:43]2[C:55](=[O:56])[C:54]3[S:53][C:52]4[CH2:51][CH2:50][CH2:49][CH2:48][C:47]=4[C:46]=3[CH:45]=[N:44]2)[C:38]=1[CH:57]=[O:58].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.O.O.C([O-])(=O)C.[Na+]>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(#N)C>[CH3:1][N:2]1[C:3](=[O:35])[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH:30]4[CH2:33][O:32][CH2:31]4)[CH2:26][C@@H:25]3[CH3:34])=[CH:20][N:19]=2)=[CH:5][C:6]([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([N:43]3[C:55](=[O:56])[C:54]4[S:53][C:52]5[CH2:51][CH2:50][CH2:49][CH2:48][C:47]=5[C:46]=4[CH:45]=[N:44]3)[C:38]=2[CH:57]=[O:58])=[CH:7]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 23665404Sodium Acetate TrihydrateHCID 866837011-methyl-3-((5-((2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-oneHCID 866842204-Chloro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde

生成物 1

HCID 866843484-[1-Methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-{6-oxo-8-thia-4,5-diaza-tricyclo[7.4.0.02,7]tri-deca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde

試薬・触媒・溶媒 3

HCID 962Water触媒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
100 °C

実験手順

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with (S)-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 191j (168 mg, 0.35 mmol), 4-chloro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde 124a (121 mg, 0.35 mmol), K3PO4 (148 mg, 0.70 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (13 mg, 0.0175 mmol), sodium acetate trihydrate (95 mg, 0.70 mmol), water (6 drops), and acetonitrile (10 mL). After bubbling nitrogen through the mixture for 30 minutes, it was heated at 100° C. under N2 protection for 1 h. Analysis of reaction mixture by LCMS showed completed conversion to the desired product. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane (30 mL) and water (30 mL). The aqueous layer was separated and extracted with dichloromethane (3×20 mL). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80/1 to 30/1) to afford 191k (118 mg, 51%) as yellow solid. MS-ESI: [M+H]+ 665

後処理

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the mixture for 30 minutes
  3. customAnalysis of reaction mixture by LCMS

出典と根拠

ORDレコード
ord-588e0a31c5d842f1840e8fa867b6ec5a
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

読み込み中…