Potassium Phosphate, Tribasic → [4-(5-{[6-(2-{[(Tert-butoxy)carbonyl]amino}ethoxy)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate

HRID 1774621Notes

Reaction equation

HRID 1774621 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15]([O:17][CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:14]=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:28]([O:31][CH2:32][C:33]1[C:34]([N:42]2[CH2:53][CH2:52][N:51]3[C:44](=[CH:45][C:46]4[CH2:47][C:48]([CH3:55])([CH3:54])[CH2:49][C:50]=43)[C:43]2=[O:56])=[N:35][CH:36]=[CH:37][C:38]=1B(O)O)(=[O:30])[CH3:29].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[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].CC#N.O>[C:28]([O:31][CH2:32][C:33]1[C:34]([N:42]2[CH2:53][CH2:52][N:51]3[C:44](=[CH:45][C:46]4[CH2:47][C:48]([CH3:55])([CH3:54])[CH2:49][C:50]=43)[C:43]2=[O:56])=[N:35][CH:36]=[CH:37][C:38]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([O:17][CH2:18][CH2:19][NH:20][C:21]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:27])[N:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:30])[CH3:29]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86684340[4-(Dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetateHCID 118116413Tert-butyl 2-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)ethylcarbamate

Product 1

HCID 118117153[4-(5-{[6-(2-{[(Tert-butoxy)carbonyl]amino}ethoxy)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetateYield 50%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
95 °C

Procedure

A 50 mL round-bottomed flask equipped with a reflux condenser was charged with 101b (500 mg, 1.14 mmol), [4-(dihydroxyboranyl)-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-3-yl]methyl acetate 101c (452 mg, 1.14 mmol), K3PO4 (483 mg, 2.28 mmol), NaOAc (187 mg, 2.28 mmol), Pd(dppf)Cl2 (42 mg, 0.057 mmol), and CH3CN/H2O (20.0/0.5 mL). The system was subject to three cycles of vacuum/argon flush then heated at 95° C. under N2 for 1 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by silica-gel column-chromatography eluting with DCM/MeOH (70:1 to 30:1) to afford 101d (400 mg, 50%) as yellow solid. MS-ESI: [M+H]+ 712.3

Workup

  1. customA 50 mL round-bottomed flask equipped with a reflux condenser
  2. customflush
  3. temperatureThe reaction mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica-gel column-chromatography
  6. washeluting with DCM/MeOH (70:1 to 30:1)

Sources & evidence

ORD record
ord-0d063457200d42fdbe29b1bb7960c20d
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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