Sodium Carbonate → HCID 70872739, compound

HRID 1616498Notes

Reaction equation

HRID 1616498 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:22]([CH2:29][CH3:30])[CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:5]([CH3:21])=[C:6]([CH:20]=1)[C:7]([NH:9][CH2:10][C:11]1[C:12](=[O:19])[NH:13][C:14]([CH3:18])=[CH:15][C:16]=1[CH3:17])=[O:8].[O:31]1[CH2:36][CH2:35][N:34]([CH2:37][C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)[CH2:33][CH2:32]1.C([O-])([O-])=O.[Na+].[Na+].O1CCO[CH2:61][CH2:60]1.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>[CH2:29]([N:22]([CH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[C:4]1[C:5]([CH3:21])=[C:6]([C:7]([NH:9][CH2:10][C:11]2[C:12](=[O:19])[NH:13][C:14]([CH3:18])=[CH:15][C:16]=2[CH2:17][CH2:60][CH3:61])=[O:8])[CH:20]=[C:2]([C:41]2[CH:40]=[CH:39][C:38]([CH2:37][N:34]3[CH2:35][CH2:36][O:31][CH2:32][CH2:33]3)=[CH:43][CH:42]=2)[CH:3]=1)[CH3:30]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27955024-((Morpholino)methyl)phenylboronic acid pinacol esterHCID 218864351,4-Dioxane--water (1/1)HCID 665767905-Bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide

Product 1

HCID 70872739HCID 70872739, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide (0.3 g, 0.59 mmol) and 4-((morpholino)methyl)phenylboronicacid pinacol ester (0.22 g, 0.71 mmol) in dioxane/water mixture (5 mL+1 mL), Na2CO3 (0.23 g, 2.14 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (0.068 g, 0.059 mmol) was added and argon was purged again for 10 min. Reaction mass was heated at 100° C. for 4 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 (0.25 g, 70%). LCMS: 601.55 (M+1)+; HPLC: 97.21% (@ 210-370 nm) (Rt; 4.380; Method: Column: YMC ODS-A 150 mm×4.6 mm×5μ; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 μL, Col. Temp.: 30° C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) δ 11.46 (bs, 1H), 8.16 (bs, 1H), 7.57 (d, 2H, J=7.6 Hz), 7.38 (t, 3H, J=6.8 Hz), 7.21 (s, 1H), 5.89 (s, 1H), 4.30 (m, 2H), 3.84-3.82 (m, 2H), 3.57 (bs, 3H), 3.48 (s, 3H), 3.28-3.22 (m, 2H), 3.09-3.02 (m, 3H), 2.36 (bs, 4H), 2.25 (s, 3H), 2.11 (s, 3H), 1.67-1.54 (m, 6H), 0.93 (t, 3H, J=7 Hz), 0.84 (t, 3H). 2H merged in solvent peak.

Workup

  1. customsolution was 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-c6fc4ec9232049abbed6e4515d72f14b
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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