Nitrogen → HCID 66990918, compound

HRID 2367435Notes

Reaction equation

HRID 2367435 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][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:11]2)[CH:3]=1.[C:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][C:33]=1[F:41])#[N:31].C([O-])(O)=O.[Na+].N#N>O1CCOCC1.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:30]([C:32]1[CH:37]=[CH:36][C:35]([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][CH2:23][C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)=[O:21])[CH2:11]3)[CH:3]=2)=[CH:34][C:33]=1[F:41])#[N:31]

Participants

7

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 86659195HCID 86659195, compound

Product 1

HCID 66990918HCID 66990918, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of cis-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-N-(phenylmethyl)-6-(trifluoromethyl)-3-piperidinecarboxamide (100 mg, 0.234 mmol) and (4-cyano-3-fluorophenyl)boronic acid (57.8 mg, 0.351 mmol) in 1,4-dioxane (2 mL) was added saturated aqueous NaHCO3, and N2 gas was bubbled through the mixture for 10 minutes into a 5 mL microwave vial. Pd(Ph3P)4 (40.5 mg, 0.035 mmol) was added, and N2 gas was bubbled through the mixture for an additional 5 minutes. The vial was capped, and the reaction mixture was heated overnight over a hot plate at 100° C. The reaction was diluted with water (5 mL), and the resulting mixture was extracted with EtOAc (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The resulting yellow oil was purified on Biotage SNAP 10 g column with gradient of 0 to 40% EtOAc in Hexane over 30 minutes to afford the title compound (66 mg) as a yellow oil. LC-MS (ES) m/z=513 [M+H]+.

Workup

  1. customwas bubbled through the mixture for 10 minutes into a 5 mL microwave vial
  2. customN2 gas was bubbled through the mixture for an additional 5 minutes
  3. customThe vial was capped
  4. additionThe reaction was diluted with water (5 mL)
  5. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting yellow oil was purified on Biotage SNAP 10 g column with gradient of 0 to 40% EtOAc in Hexane over 30 minutes

Sources & evidence

ORD record
ord-a0c7b654e4ba4c4b9a71c7d97f880844
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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