Potassium Phosphate, Tribasic → 3-[1-Methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridine-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde

HRID 592543Notes

Reaction equation

HRID 592543 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:10]2[CH2:21][CH2:20][C:19]3[C:18]4[CH2:17][C:16]([CH3:23])([CH3:22])[CH2:15][C:14]=4[S:13][C:12]=3[C:11]2=[O:24])[C:7]=1[CH:8]=[O:9].[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][CH2:49]3)=[CH:44][N:43]=2)[C:27]1=[O:58].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.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]>[CH3:25][N:26]1[C:27](=[O:58])[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][CH2:49]3)=[CH:44][N:43]=2)=[CH:29][C:30]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([N:10]3[CH2:21][CH2:20][C:19]4[C:18]5[CH2:17][C:16]([CH3:23])([CH3:22])[CH2:15][C:14]=5[S:13][C:12]=4[C:11]3=[O:24])[C:7]=2[CH:8]=[O:9])=[CH:31]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839131-methyl-3-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2(1H)-oneHCID 866841773-Bromo-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehyde

Product 1

HCID 866841783-[1-Methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridine-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]-5-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8), 2(6)-dien-10-yl}pyridine-4-carbaldehydeYield 40%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A sealed tube was charged with 106i (200 mg, 0.50 mmol), 1-methyl-3-(5-(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 101l (240 mg, 0.51 mmol), PdCl2(dppf) (42 mg, 0.05 mmol), K3PO4 (230 mg, 1 mmol), and NaOAc (80 mg, 1 mmol) in CH3CN (5 mL) and H2O (1.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 10:1 DCM/MeOH to afford 106j (130 mg, 40%) as a pale yellow solid. MS: [M+H]+ 666.

Workup

  1. customThe system was evacuated
  2. additionrefilled with N2
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by flash column chromatography
  7. washeluting with 10:1 DCM/MeOH

Sources & evidence

ORD record
ord-f4ef4d9fa4934347afde9614772be59b
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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