Sodium Carbonate → (R)-N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}-2-methylpropane-2-sulfinamide

HRID 2207411Notes

Reaction equation

HRID 2207411 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:35]1[CH:36]=[CH:37][C:38]([C:41]([CH:52]2[CH2:54][CH2:53]2)([CH:49]2[CH2:51][CH2:50]2)[NH:42][S@@:43]([C:45]([CH3:48])([CH3:47])[CH3:46])=[O:44])=[N:39][CH:40]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:49]1([C:41]([CH:52]2[CH2:54][CH2:53]2)([C:38]2[CH:37]=[CH:36][C:35]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[N:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][N:19]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:40][N:39]=2)[NH:42][S@@:43]([C:45]([CH3:47])([CH3:48])[CH3:46])=[O:44])[CH2:51][CH2:50]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 131735913(R)-N-[(5-bromopyridin-2-yl)(dicyclopropyl)methyl]-2-methylpropane-2-sulfinamide

Product 1

HCID 131735914(R)-N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Procedure

N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (300 mg, 0.791 mmol), PdCl2(dppf)-dichloromethane adduct (32.3 mg, 0.040 mmol), and sodium carbonate (2 M, 0.791 mL, 1.58 mmol) were added to a solution of (R)—N-[(5-bromopyridin-2-yl)(dicyclopropyl)methyl]-2-methylpropane-2-sulfinamide (344 mg, 0.926 mmol) in 2-methyl-THF (2.60 mL) and flushed and purged with Ar(g). The reaction mixture was irradiated in a microwave reactor for 5 minutes at 170° C. Upon cooling, the reaction mixture was diluting with saturated aqueous NaHCO3 (10.0 mL) and extracted with ethyl acetate (20.0 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by silica gel chromatography (0.5-3% methanol in dichloromethane) to yield (R)—N-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}-2-methylpropane-2-sulfinamide. MS APCI calc'd for C28H33F3N5OS [M+H]+ 544. found 544.

Workup

  1. customflushed
  2. custompurged with Ar(g)
  3. customThe reaction mixture was irradiated in a microwave reactor for 5 minutes at 170° C
  4. temperatureUpon cooling
  5. additionthe reaction mixture was diluting with saturated aqueous NaHCO3 (10.0 mL)
  6. extractionextracted with ethyl acetate (20.0 mL)
  7. washThe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography (0.5-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-074ab25856de4f91a21cd56d8f81598c
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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