Nitrogen → HCID 66991246, compound

HRID 2367430Notes

Reaction equation

HRID 2367430 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[CH2:27][CH2:26][CH2:25][CH2:24]3)=[O:21])[CH2:11]2)[CH:3]=1.[C:28]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][C:31]=1[F:39])#[N:29].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:28]([C:30]1[CH:35]=[CH:34][C:33]([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[CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:21])[CH2:11]3)[CH:3]=2)=[CH:32][C:31]=1[F:39])#[N:29]

Participants

7

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 86659193HCID 86659193, compound

Product 1

HCID 66991246HCID 66991246, compoundYield 66.8%

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-cyclopentyl-6-(trifluoromethyl)-3-piperidinecarboxamide (46 mg, 0.113 mmol) and (4-cyano-3-fluorophenyl)boronic acid (28.0 mg, 0.170 mmol) in 1,4-dioxane (1 mL) was added saturated aqueous NaHCO3 (0.5 mL), and N2 gas was bubbled through the resulting mixture for 10 minutes into a 5 mL sealable vial. Pd(Ph3P)4 (19.7 mg, 0.017 mmol) was added, and N2 was bubbled for an additional 5 minute. The vial was capped, and the reaction mixture was heated at 100° C. overnight. The reaction was diluted with water (5 mL) and then extracted with EtOAc (3×10 mL). The organics were dried over MgSO4, filtered and concentrated. The resulting yellow oil was then purified on Biotage SNAP column 10 g with gradient of 0 to 40% EtOAc in Hexane to afford the title compound (37 mg) as a yellow oil. LC-MS (ES) m/z=491 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-71949a2ea986444d83eef0a9dc3e821c
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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