Sodium Carbonate → HCID 69871063, compound

HRID 2229005Notes

Reaction equation

HRID 2229005 reaction equation
[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26](B4OC(C)(C)C(C)(C)O4)=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:10][CH:9]=1)[CH3:6])[CH3:2].Br[C:41]1[CH:42]=[N:43][CH:44]=[N:45][CH:46]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)C>[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:24]=[CH:25][C:26]([C:41]4[CH:42]=[N:43][CH:44]=[N:45][CH:46]=4)=[CH:27][CH:28]=3)[O:20][C:21]=2[CH3:22])=[CH:10][CH:9]=1)[CH3:6])[CH3:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 783445-BromopyrimidineHCID 23589997HCID 23589997, compound

Product 1

HCID 69871063HCID 69871063, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
86 °C

Procedure

A 50 mL flask was charged with 2-methyl-2-[4-(2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazol-4-yl}-ethoxy)-phenoxy]-propionic acid ethyl ester (198 mg, 0.371 mmol), 5-bromopyrimidine (54 mg, 338 mmol), and 5 mL of isopropanol. The flask was purged with N2 three times. After 20 min, palladium acetate (3.0 mg, 0.04 mmol) and triphenylphosphine (3.5 mg, 0.04 mmol) were added. Following addition of a solution of sodium carbonate (43 mg in 1 mL H2O), the mixture was heated to 86° C. for 4 h. The solvent was removed under reduced pressure and the remaining residue taken up in CH2Cl2 (25 mL) and extracted with 0.5 N NaOH (25 mL). The aqueous layer was back extracted with an additional 25 mL CH2Cl2 and the organic layers combined. The organic layer was washed with 1 N NaOH (25 mL) and H2O (25 mL) and then dried and concentrated in vacuo. Flash chromatography provided the desired product. 1H NMR (400 MHz, CDCl3) δ9.23 (s, 1H), 9.20 (s, 2H), 8.16 (d, 2H), 7.65 (d, 2H), 6.88 (d, 2H), 6.75 (d, 2H), 4.21 (q, 2H), 4.20 (t, 2H), 3.00 (t, 2H), 2.39 (s, 3H), 1.48 (s, 6H), 1.21 (t, 3H); MS (EI) 4.88.1 (M+H)+.

Workup

  1. customThe flask was purged with N2 three times
  2. customThe solvent was removed under reduced pressure
  3. extractionextracted with 0.5 N NaOH (25 mL)
  4. extractionThe aqueous layer was back extracted with an additional 25 mL CH2Cl2
  5. washThe organic layer was washed with 1 N NaOH (25 mL) and H2O (25 mL)
  6. customdried
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb86930d0b9242c6b6d02cf731828c7a
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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