Sodium Carbonate → Tert-butyl (1-{4-cyano-2-ethoxy-5-methyl-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate

HRID 510994Notes

Reaction equation

HRID 510994 reaction equation
Cl[C:2]1[C:3]([C:31]#[N:32])=[C:4]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:26]=2)[C:5]([O:18][CH2:19][CH3:20])=[C:6]([CH:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])[CH:7]=1.[CH3:33]B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.Cl[Pd](Cl)(P(C(C)(C)C)(C(C)(C)C)C1C=CC(N(C)C)=CC=1)P(C1C=CC(N(C)C)=CC=1)(C(C)(C)C)C(C)(C)C>[C:31]([C:3]1[C:2]([CH3:33])=[CH:7][C:6]([CH:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[C:5]([O:18][CH2:19][CH3:20])[C:4]=1[C:21]1[CH:22]=[N:23][CH:24]=[C:25]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:26]=1)#[N:32]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 86666906Tert-butyl (1-{5-chloro-4-cyano-2-ethoxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate

Product 1

HCID 86666909Tert-butyl (1-{4-cyano-2-ethoxy-5-methyl-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamateYield 65.3%

Reagents, catalysts & solvents 3

HCID 178482906HCID 178482906, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To tert-butyl (1-{5-chloro-4-cyano-2-ethoxy-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate (60 mg, 0.1 mmol) and methylboronic acid (6.4 mg, 0.11 mmol) in 1,4-dioxane (4 mL) was added sodium carbonate (20 mg, 0.2 mmol) in water (2 mL). The reaction was degassed with N2. Dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl})palladium (4 mg, 0.005 mmol) was added and degassed again with N2. The reaction was heated at 90° C. overnight. The reaction was allowed to cool to room temperature and was partitioned between EtOAc and water. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give crude product. The product was purified by chromatography on silica gel eluting with a hexane: EtOAc gradient to give tert-butyl (1-{4-cyano-2-ethoxy-5-methyl-3-[5-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)carbamate as a yellow oil (0.030 g, 50%). LCMS calculated for C23H30N3O5S (M+H)+: m/z=460.1. found: 460.2.

Workup

  1. customThe reaction was degassed with N2
  2. customdegassed again with N2
  3. temperatureto cool to room temperature
  4. customwas partitioned between EtOAc and water
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude product
  10. customThe product was purified by chromatography on silica gel eluting with a hexane

Sources & evidence

ORD record
ord-0c2e231c3c064dab9565b853ee9f3f35
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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