Sodium Carbonate → HCID 70872426, compound

HRID 1959296Notes

Reaction equation

HRID 1959296 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:17][C:18]1[CH:23]=[C:22]([CH3:24])[NH:21][C:20](=[O:25])[C:19]=1[CH2:26][NH:27][C:28](=[O:54])[C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[C:31]([N:44]([CH2:51][CH3:52])[CH:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[C:30]=1[CH3:53].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[C:7]([C:6]1[CH:9]=[C:2]([C:33]2[CH:32]=[C:31]([N:44]([CH2:51][CH3:52])[CH:45]3[CH2:50][CH2:49][O:48][CH2:47][CH2:46]3)[C:30]([CH3:53])=[C:29]([C:28]([NH:27][CH2:26][C:19]3[C:20](=[O:25])[NH:21][C:22]([CH3:24])=[CH:23][C:18]=3[CH3:17])=[O:54])[CH:34]=2)[CH:3]=[CH:4][C:5]=1[CH2:10][N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)#[N:8]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 59558570HCID 59558570, compoundHCID 70872817HCID 70872817, compound

Product 1

HCID 70872426HCID 70872426, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-bromo-2-(morpholinomethyl)benzonitrile (190 mg, 0.68 mmol) and N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (200 mg, 0.45 mmol) in dioxane (6 mL), aqueous 2M Na2CO3 solution (0.81 mL, 1.63 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (52 mg, 0.04 mmol) was added and argon was purged again for 15 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 (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the title compound (16 mg, 6%). LCMS: 598.20 (M+1)+; HPLC: 89.15% (@254 nm) (Rt; 4.039; 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), 8.20 (t, 1H), 8.15 (s, 1H), 7.94 (d, 1H, J=6.8 Hz), 7.63 (d, 1H, J=8.4 Hz), 7.51 (s, 1H), 7.31 (s, 1H), 5.86 (s, 1H), 4.29 (m, 2H), 3.84-3.82 (m, 2H), 3.66-3.58 (m, 6H), 3.32 (m, 5H), 3.11-3.03 (m, 4H), 2.25 (s, 3H), 2.21 (s, 3H), 2.11 (s, 3H), 1.65-1.51 (m, 4H), 0.82 (t, 3H, J=6 Hz).

Workup

  1. customsolution was purged with argon for 15 min
  2. customargon was purged again for 15 min
  3. customReaction mass
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM (3 times)
  6. dry with materialCombined organic layer was dried over sodium sulphate
  7. customRemoval of the solvent under reduced pressure
  8. customfollowed by column chromatographic purification

Sources & evidence

ORD record
ord-58f27764be9d4e80b7758cc55eeae324
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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