Sodium Bicarbonate → (3S,6R)-1-[6-(4-Cyano-3,5-difluorophenyl)-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide

HRID 2367644Notes

Reaction equation

HRID 2367644 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([NH:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:11]2)[CH:3]=1.[C:27]([C:29]1[C:34]([F:35])=[CH:33][C:32](B(O)O)=[CH:31][C:30]=1[F:39])#[N:28].C([O-])(O)=O.[Na+]>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:27]([C:29]1[C:34]([F:35])=[CH:33][C:32]([C:2]2[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]3[C@H:15]([CH3:16])[CH2:14][CH2:13][C@H:12]([C:17]([NH:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:11]3)[CH:3]=2)=[CH:31][C:30]=1[F:39])#[N:28]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 55252910(4-Cyano-3,5-difluorophenyl)boronic acidHCID 58504823(3S,6R)-1-[6-Chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide

Product 1

HCID 58504827(3S,6R)-1-[6-(4-Cyano-3,5-difluorophenyl)-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(3S,6R)-1-[6-chloro-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (100 mg, 0.267 mmol) and (4-cyano-3,5-difluorophenyl)boronic acid (73.4 mg, 0.401 mmol) were dissolved in 1,4-Dioxane (2 mL) in a 5 mL sealable vial then added saturated NaHCO3 (1 mL). Nitrogen gas was bubbled through the mixture for 10 min. Then Pd(Ph3P)4 (37.1 mg, 0.032 mmol) was added and nitrogen gas bubbled for an additional 5 min. The vial was capped the reaction was heat at 100° C. overnight. The reaction was diluted with water (5 mL) and then extracted with EtOAc (3×10 mL). Organic were combined, dried over MgSO4, filtered and concentrated. The yellow oil was then purified on a 10 g Biotage SNAP column with gradient of 0 to 40% EtOAc in Hexane. LC-MS (ES) m/z=477 [M+H]+.

Workup

  1. customNitrogen gas was bubbled through the mixture for 10 min
  2. customnitrogen gas bubbled for an additional 5 min
  3. customThe vial was capped the reaction
  4. additionThe reaction was diluted with water (5 mL)
  5. extractionextracted with EtOAc (3×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe yellow oil was then purified on a 10 g Biotage SNAP column with gradient of 0 to 40% EtOAc in Hexane

Sources & evidence

ORD record
ord-0a810ca9184f4d76afe7a0b73b43224e
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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