Sodium Carbonate → methyl 5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxylate

HRID 1616499Notes

Reaction equation

HRID 1616499 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:13]([CH2:20][CH3:21])[CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[O:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[CH2:24][CH2:23]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[CH2:20]([N:13]([CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)[C:4]1[C:5]([CH3:12])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=[C:2]([C:32]2[CH:31]=[CH:30][C:29]([CH2:28][N:25]3[CH2:26][CH2:27][O:22][CH2:23][CH2:24]3)=[CH:34][CH:33]=2)[CH:3]=1)[CH3:21]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27955024-((Morpholino)methyl)phenylboronic acid pinacol esterHCID 70872485methyl 5-bromo-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate

Product 1

HCID 70872958methyl 5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxylateYield 59%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of methyl 5-bromo-3-(ethyl-(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoate (1 g, 2.82 mmol) and 4-((morpholino)methyl)phenylboronic acid pinacol ester (1.03 g, 3.38 mmol) in dioxane/water mixture (10 mL+2 mL), Na2CO3 (1.08 g, 10.14 mmol) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.325 g, 0.28 mmol) was added and argon was purged again for 10 min. Reaction mass was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to afford crude material which was purified by column chromatography over silica gel to afford the title compound (0.75 g, 59%).

Workup

  1. customsolution purged with argon for 15 min
  2. customargon was purged again for 10 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM
  6. dry with materialCombined organic layers were dried over Na2SO4 and solvent
  7. customremoved under reduced pressure
  8. customto afford crude material which
  9. customwas purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-394292dbc50a4497a1a0db2f9232ad59
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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