Ethanol → HCID 89560529, compound

HRID 1747213Notes

Reaction equation

HRID 1747213 reaction equation
Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][C@H:16]1[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].CCO.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][C@H:16]1[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([C:2]2[N:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:27]=1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 783452-BromopyrimidineHCID 131733556HCID 131733556, compound

Product 1

HCID 89560529HCID 89560529, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromopyrimidine (43 mg, 0.27 mmol) was added in one portion to a RT solution of (R)-3-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-morpholine-4-carboxylic acid tert-butyl ester B-7 (100 mg, 0.25 mmol) in dioxane (0.76 mL) under argon. EtOH (0.38 mL) was then added followed by 2M aq. Na2CO3 (0.38 mL, 0.74 mmol) and argon was bubbled through the resulting suspension for 1 min. Pd(dppf)Cl2.DCM (12 mg, 6 mol %) was added in one portion and the resulting mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to RT, quenched into water and filtered through a celite plug washing with TBME. The layers were separated and the aqueous phase was extracted with TBME (3×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered through a second celite plug and evaporated in vacuo to give the crude product that was purified by prep. HPLC (method E) to give the title compound as a yellow oil. LC-MS B: tR=0.79 min; [M+H]+=356.05.

Workup

  1. customwas bubbled through the resulting suspension for 1 min
  2. additionDCM (12 mg, 6 mol %) was added in one portion
  3. temperatureThe reaction mixture was cooled to RT
  4. customquenched into water
  5. filtrationfiltered through a celite plug
  6. washwashing with TBME
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with TBME (3×)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered through a second celite plug
  12. customevaporated in vacuo
  13. customto give the crude product that
  14. customwas purified by prep

Sources & evidence

ORD record
ord-491cb42e66fb44aa9ed107a47c5276e2
Source dataset
uspto-grants-2015_10
Patent number
US09150566B2

Reaction notes

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