Potassium Phosphate, Tribasic → HCID 86727570, compound

HRID 519167Notes

Reaction equation

HRID 519167 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH:10]([CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][C@H:24]1[N:37]2[C:28]([CH2:29][O:30][C:31]3[C:36]2=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=3)=[N:27][NH:26][C:25]1=[O:47].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:34]2[CH:35]=[C:36]3[C:31](=[CH:32][CH:33]=2)[O:30][CH2:29][C:28]2[N:37]3[C@H:24]([CH3:23])[C:25](=[O:47])[NH:26][N:27]=2)[CH:10]([CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 86671561HCID 86671561, compoundHCID 86727453HCID 86727453, compound

Product 1

HCID 86727570HCID 86727570, compoundYield 104%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-methyl-4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Preparation #13, 5.07 g, 14.69 mmol), (R)-4-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #11, Step E, 2.8 g, 8.16 mmol) and K3PO4 (3.46 g, 16.32 mmol) in DMF (60 mL) and water (10 mL) was added Pd(Ph3P)4 (3.77 g, 3.26 mmol). The reaction mixture was stirred at 80° C. overnight then cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3-50% EtOAc in petroleum ether) to give 3-methyl-4-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.5 g) as a yellow liquid. Further purification by prep-HPLC (Table 3, Method 33) ave 3-methyl-4-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.5 g, 44%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 8.03 (brs, 1H), 7.02-6.93 (m, 2H), 6.87 (s, 1H), 5.81 (brs, 1H), 4.77 (q, J=6.8 Hz, 1H), 4.66-4.53 (d, J=13.2 Hz, 2H), 4.47-4.18 (m, 1H), 3.95-3.77 (m, 2H), 3.32 (d, J=13.2 Hz, 1H), 2.79 (brs, 1H), 1.53 (m, 3H), 1.51 (s, 9H), 1.02 (d, J=6.8 Hz, 3H). LC/MS (Table 1, Method 44) Rt=3.339 min.; MS m/z: 414 [M+H]+.

Workup

  1. temperaturethen cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluting with 3-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-96a046b89b3a417a835618d6c7bf6e6b
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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