Sodium Carbonate → HCID 89865820, compound

HRID 2207714Notes

Reaction equation

HRID 2207714 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][CH:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[O:18][CH2:19][CH2:20][O:21][C:13]=23)[CH3:11])[CH:3]=1.[CH3:22][NH:23][C:24]1[N:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][N:25]=1.C([O-])([O-])=O.[Na+].[Na+]>CC(O)C.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[O:21]1[C:13]2[C:14](=[N:15][CH:16]=[CH:17][C:12]=2[C@H:10]([CH3:11])[CH2:9][NH:8][C:4]2[N:5]=[CH:6][N:7]=[C:2]([C:27]3[CH:26]=[N:25][C:24]([NH:23][CH3:22])=[N:29][CH:28]=3)[CH:3]=2)[O:18][CH2:19][CH2:20]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 467396412-Methylaminopyrimidine-5-boronic acid, pinacol esterHCID 89858366HCID 89858366, compound

Product 1

HCID 89865820HCID 89865820, compound

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

As shown in step 7-vi of Scheme 7, 6-chloro-N-[2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl)propyl]pyrimidin-4-amine (410 mg) was dissolved in IPA (0.75 mL). N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (23 mg) was added, followed by the addition of 2M Na2CO3 (122 μL) and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (7 mg). The reaction vessel was sealed and heated at 80° C. overnight. The mixture was cooled, diluted with ethyl acetate, washed with water, dried over Na2SO4, filtered, concentrated under reduced pressure and purified by reversed-phase HPLC, 5-50% ACN/H2O/0.1% TFA. Fractions containing pure product were collected, dissolved in MeOH, passed through a carbonate cartridge, and concentrated under reduced pressure to provide (S)—N6-(2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl)propyl)-N2′-methyl-[4,5′-bipyrimidine]-2′,6-diamine (Compound 462): ESMS=380.39 (M+H); 1H NMR (300 MHz, methanol-d4) δ 8.75 (s, 2H), 8.47 (s, 1H), 7.65 (d, J=5.3 Hz, 1H), 6.94 (d, J=5.2 Hz, 1H), 6.76 (s, 1H), 4.46-4.34 (m, 2H), 4.32-4.19 (m, 2H), 3.59 (ddd, J=12.0, 11.5, 7.3 Hz, 3H), 2.99 (s, 3H), 1.32 (d, J=6.7 Hz, 3H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe mixture was cooled
  3. washwashed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by reversed-phase HPLC, 5-50% ACN/H2O/0.1% TFA
  8. additionFractions containing pure product
  9. customwere collected
  10. dissolutiondissolved in MeOH
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-67e00562cda44184ad69ee92e4fac8ea
Source dataset
uspto-grants-2016_06
Patent number
US09376448B2

Reaction notes

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