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 1411742노트

반응식

HRID 1411742 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 962Water촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-5dda33c066684c36af5d7632c18828eb
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921353B2

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