Sodium Bicarbonate → HCID 66990755, compound

HRID 2367237Notes

Reaction equation

HRID 2367237 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][NH:12][C:13]1[N:18]=[C:17]([N:19]2[C@H:24]([C:25]([F:28])([F:27])[F:26])[CH2:23][CH2:22][C@H:21]([C:29]([NH:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:30])[CH2:20]2)[CH:16]=[C:15](Cl)[N:14]=1.[C:39]([C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][C:42]=1[F:50])#[N:40].C([O-])(O)=O.[Na+]>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.O1CCOCC1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][NH:12][C:13]1[N:18]=[C:17]([N:19]2[C@H:24]([C:25]([F:28])([F:27])[F:26])[CH2:23][CH2:22][C@H:21]([C:29]([NH:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:30])[CH2:20]2)[CH:16]=[C:15]([C:44]2[CH:45]=[CH:46][C:41]([C:39]#[N:40])=[C:42]([F:50])[CH:43]=2)[N:14]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 86659172HCID 86659172, compound

Product 1

HCID 66990755HCID 66990755, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To cis-1-[2-({[2,4-bis(methyloxy)phenyl]methyl}amino)-6-chloro-4-pyrimidinyl]-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (322 mg, 0.58 mmol) and (4-cyano-3-fluorophenyl)boronic acid (124 mg, 0.75 mmol) were added 1,4-dioxane (6 mL) and saturated aqueous NaHCO3 (3 mL), and the resulting mixture was purged (“degassed”) with N2 into a sealable tube for 5 minutes. Pd(Ph3P)4 (33.5 mg, 0.029 mmol) was added, and N2 gas was bubbled through the mixture for an additional 5 minutes. The tube was sealed, and the reaction mixture was stirred overnight at 100° C. The reaction mixture was poured onto water and EtOAc. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% Hexanes to 50% EtOAc/Hexanes) afforded the title compound (305 mg) as a yellow foam. LC-MS (ES) m/z=641 [M+H]+.

Workup

  1. customthe resulting mixture was purged
  2. custom(“degassed”) with N2 into a sealable tube for 5 minutes
  3. customN2 gas was bubbled through the mixture for an additional 5 minutes
  4. customThe tube was sealed
  5. additionThe reaction mixture was poured onto water and EtOAc
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9417259ea3c441e5a374e89b38806de9
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…