Sodium Bicarbonate → HCID 66990661, compound

HRID 2367241Notes

Reaction equation

HRID 2367241 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][C@H:12]([C:20]([NH:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[O:21])[CH2:11]2)[CH:3]=1.[C:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][C:32]=1[F:40])#[N:30].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>[C:29]([C:31]1[CH:36]=[CH:35][C:34]([C:2]2[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]3[C@H:15]([C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][C@H:12]([C:20]([NH:22][CH:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)=[O:21])[CH2:11]3)[CH:3]=2)=[CH:33][C:32]=1[F:40])#[N:30]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 86659173HCID 86659173, compound

Product 1

HCID 66990661HCID 66990661, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To cis-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (204 mg, 0.486 mmol) and (4-cyano-3-fluorophenyl)boronic acid (104 mg, 0.632 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 (28 mg, 0.024 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. The precipitate formed was filtered. EtOAc was added to the solid in the filter, and the mixture was stirred gently with a spatula until the solid dissolved. The resulting solution was filtered, and the filtrate was dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% Hexanes to 50% EtOAc/Hexanes) afforded the title compound (152 mg) as a yellow foam. LC-MS (ES) m/z=505 [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
  6. customThe precipitate formed
  7. filtrationwas filtered
  8. additionEtOAc was added to the solid in the filter
  9. stirringthe mixture was stirred gently with a spatula until the solid
  10. dissolutiondissolved
  11. filtrationThe resulting solution was filtered
  12. dry with materialthe filtrate was dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-94b3eb0ba01745bf8cbcfdcabd7717ec
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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