Potassium Phosphate, Tribasic → 2-{4,4-Dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}-4-(5-{[5-(2-methoxyethyl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridine-3-carbaldehyde

HRID 593107Notes

Reaction equation

HRID 593107 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[N:19]=[CH:18][C:17]3[C:16]4[CH2:15][C:14]([CH3:21])([CH3:20])[CH2:13][C:12]=4[S:11][C:10]=3[C:9]2=[O:22])[C:3]=1[CH:23]=[O:24].[CH3:25][O:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][N:32]2[N:35]=[C:36]([NH:38][C:39]3[C:40](=[O:55])[N:41]([CH3:54])[CH:42]=[C:43](B4OC(C)(C)C(C)(C)O4)[CH:44]=3)[CH:37]=[C:31]2[CH2:30]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].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>[CH3:20][C:14]1([CH3:21])[CH2:13][C:12]2[S:11][C:10]3[C:9](=[O:22])[N:8]([C:4]4[C:3]([CH:23]=[O:24])=[C:2]([C:43]5[CH:44]=[C:39]([NH:38][C:36]6[CH:37]=[C:31]7[CH2:30][N:29]([CH2:28][CH2:27][O:26][CH3:25])[CH2:34][CH2:33][N:32]7[N:35]=6)[C:40](=[O:55])[N:41]([CH3:54])[CH:42]=5)[CH:7]=[CH:6][N:5]=4)[N:19]=[CH:18][C:17]=3[C:16]=2[CH2:15]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839943-(5-(2-Methoxyethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866845164-Chloro-2-{4,4-dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}pyridine-3-carbaldehyde

Product 1

HCID 866845512-{4,4-Dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}-4-(5-{[5-(2-methoxyethyl)-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridine-3-carbaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 4-chloro-2-{4,4-dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}pyridine-3-carbaldehyde 282i (60 mg, 0.167 mmol), 304d (143.4 mg, 0.334 mmol), Pd(dppf)Cl2 (6.8 mg, 0.0084 mol), K3PO4 (70.8 mg, 0.334 mmol), sodium acetate (27.4 mg, 0.334 mmol), acetonitrile (10 mL), and water (3 drops). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100° C. for 1 h under N2 protection. Analysis of reaction mixture by LCMS showed complete conversion to the desired product. It was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 304e (80 mg, 77%) as white solid. MS-ESI: [M+H]+ 626.8

Workup

  1. customA 50-mL round-bottomed flask equipped with a reflux condenser
  2. customflush
  3. customAnalysis of reaction mixture by LCMS

Sources & evidence

ORD record
ord-de30cdd1a2fb4674a1e7945c9e992d36
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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