Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(1-methyl-5-{[6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naph-thyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl)methyl Acetate

HRID 1919082Notes

Reaction equation

HRID 1919082 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[CH2:17][N:16]([CH:21]4[CH2:24][O:23][CH2:22]4)[CH2:15][CH2:14][C:13]=3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:25]([O:28][CH2:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:57][CH2:56][C:55]2[C:54]3[CH2:53][C:52]([CH3:59])([CH3:58])[CH2:51][C:50]=3[S:49][C:48]=2[C:47]1=[O:60])(=[O:27])[CH3:26].CC(O[Na])=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[C:25]([O:28][CH2:29][C:30]1[C:35]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][N:16]([CH:21]5[CH2:24][O:23][CH2:22]5)[CH2:15][CH2:14][C:13]=4[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:57][CH2:56][C:55]2[C:54]3[CH2:53][C:52]([CH3:59])([CH3:58])[CH2:51][C:50]=3[S:49][C:48]=2[C:47]1=[O:60])(=[O:27])[CH3:26]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 580437985-Bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-oneHCID 67016224(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl AcetateHCID 178418247HCID 178418247, compound

Product 1

HCID 68208425(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(1-methyl-5-{[6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naph-thyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)phenyl)methyl AcetateYield 57.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A 25 mL sealed tube was charged with 5-bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-one 219a (400 mg, 1.0 mmol), (2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 247b (493 mg, 1.0 mmol), CH3COONa (168 mg, 2.0 mmol), K3PO4 (546 mg, 2.0 mmol), PdCl2(dppf) (84 mg, 0.1 mmol) suspended in CH3CN (25 mL) and H2O (1 mL). The mixture was heated at 110° C. for 2 hours. It was then evaporated and the residue was purified by column chromatography eluting with 20:1 methylene chloride/methanol (20:1) to give 280a as a brown solid (400 mg, 56%). MS: (M+H)+ 698.

Workup

  1. customA 25 mL sealed tube
  2. customIt was then evaporated
  3. customthe residue was purified by column chromatography
  4. washeluting with 20:1 methylene chloride/methanol (20:1)

Sources & evidence

ORD record
ord-654b20dfd2094fa0985af802914abbed
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…