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Sodium Acetate → 4-[1-Methyl-5-({5-[(25)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10), 8-dien-6-yl]pyridine-3-carbaldehyde

HRID 592751
Notes
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Reaction equation

HRID 592751 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[C:20](=[O:21])[C:19]3[N:11]([C:12]4[C@H:13]5[CH2:22][C@@H:16]([C:17]=4[CH:18]=3)[CH2:15][CH2:14]5)[CH2:10][CH2:9]2)[C:3]=1[CH:23]=[O:24].[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH:54]4[CH2:57][O:56][CH2:55]4)[CH2:50][C@@H:49]3[CH3:58])=[CH:44][N:43]=2)[C:27]1=[O:59].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>[CH3:25][N:26]1[C:27](=[O:59])[C:28]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH:54]4[CH2:55][O:56][CH2:57]4)[CH2:50][C@@H:49]3[CH3:58])=[CH:44][N:43]=2)=[CH:29][C:30]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([N:8]3[C:20](=[O:21])[C:19]4[N:11]([C:12]5[C@H:13]6[CH2:22][C@@H:16]([C:17]=5[CH:18]=4)[CH2:15][CH2:14]6)[CH2:10][CH2:9]3)[C:3]=2[CH:23]=[O:24])=[CH:31]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 517045Sodium AcetateHCID 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 866843014-Chloro-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde

Product 1

HCID 86684311
4-[1-Methyl-5-({5-[(25)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10), 8-dien-6-yl]pyridine-3-carbaldehyde
Yield 44%

Reagents, catalysts & solvents 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask was charged with 4-chloro-2-[(1R,11S)-7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl]pyridine-3-carbaldehyde 170b (200 mg, 0.59 mmol), 1-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)-1,2-dihydropyridin-2-one 191j (400 mg, 0.88 mmol), PdCl2(dppf) (50 mg, 0.06 mmol), K3PO43 water (300 mg, 1.20 mmol), sodium acetate (100 mg, 1.20 mmol), acetonitrile (15 mL), and water (1.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 174a as a red solid (170 mg, 44%). MS-ESI: [M+H]+ 661.3

Workup

  1. customAfter three cycles of vacuum/argon flush
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was purified with silica-gel column chromatography
  5. washeluting with 1:20 methanol/dichloromethane

Sources & evidence

ORD record
ord-ee5a530c26be4d6f93afb9493e3876e9
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09238655B2

Reaction notes

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