Sodium Carbonate → (7R)-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-5-(tetrahydro-2H-pyran-2-yloxyamino)-7,8-dihydropyrido[4,3-d]pyrimidin-2-amine

HRID 656630Notes

Reaction equation

HRID 656630 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[N:18]=[C:17]([NH:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[C:16]2[C:15]([CH3:27])=[N:14][C:13]([NH2:28])=[N:12][C:11]=2[CH2:10]1.[CH3:29][O:30][C:31]1[N:36]=[C:35](B2OCCN(C3C=CC=CC=3)CCO2)[CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C(=O)C.C(OCC)(=O)C>[F:8][C:6]1[CH:5]=[CH:4][C:3]([C@@H:9]2[N:18]=[C:17]([NH:19][O:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][O:22]3)[C:16]3[C:15]([CH3:27])=[N:14][C:13]([NH2:28])=[N:12][C:11]=3[CH2:10]2)=[C:2]([C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([O:30][CH3:29])[N:36]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 162178652-(6-Methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocaneHCID 57999098(7R)-7-(2-bromo-4-fluorophenyl)-4-methyl-5-(tetrahydro-2H-pyran-2-yloxyamino)-7,8-dihydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 57999257(7R)-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-5-(tetrahydro-2H-pyran-2-yloxyamino)-7,8-dihydropyrido[4,3-d]pyrimidin-2-amineYield 124.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

(7R)-7-(2-bromo-4-fluorophenyl)-4-methyl-5-(tetrahydro-2H-pyran-2-yloxyamino)-7,8-dihydropyrido[4,3-d]pyrimidin-2-amine (0.838 g, 1.86 mmol), 2-(6-methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocane (1.33 g, 4.47 mmol), sodium carbonate 2M solution (3.72 mL, 7.44 mmol) were combined in N,N-Dimethylacetamide (12 mL) and then the mixture was purged with nitrogen for 5 minutes. 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (0.136 g, 0.186 mmol) was then added and the reaction was heated in 85° C. oil bath overnight. Next day, the reaction was diluted with ethyl acetate 80 mL, washed with brine (80 mL), dried over sodium sulfate, and concentrated to a crude product which was then purified by flash column chromatography, SiO2, gradient 20-100% ethyl acetate/hexane to give a white solid, 1.11 g of product, contaminated with the impurity of mass 182 (byproduct from the boronic ester, compound 6). MS (ES) [M+H] calc'd for C25H27FN6O3, 479. found, 479.4.

Workup

  1. customthe mixture was purged with nitrogen for 5 minutes
  2. addition1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (0.136 g, 0.186 mmol) was then added
  3. washwashed with brine (80 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to a crude product which
  6. customwas then purified by flash column chromatography, SiO2, gradient 20-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-cdb236b169dc4d0fb392ebe82c738043
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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