Sodium Carbonate → HCID 118092639, compound

HRID 2207405Notes

Reaction equation

HRID 2207405 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([CH3:14])([CH2:12][CH3:13])[C:10]#[N:11])=[N:6][CH:7]=1.[CH3:15][C:16]1[CH:17]=[C:18]([NH:31][C:32]2[N:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=2)[CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.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>[CH3:14][C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([C:20]2[CH:19]=[C:18]([NH:31][C:32]3[N:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=3)[CH:17]=[C:16]([CH3:15])[CH:21]=2)=[CH:7][N:6]=1)([CH2:12][CH3:13])[C:10]#[N:11]

Participants

6

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 131735909HCID 131735909, compound

Product 1

HCID 118092639HCID 118092639, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Argon was bubbled through a mixture of 2-[(5-bromopyridin-2-yl)amino]-2-methylbutanenitrile (327 mg, 1.29 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (488 mg, 1.29 mmol), and sodium carbonate (2 M, 1.28 mL, 2.57 mmol) in 2-methyl-THF (6.43 mL) for ˜5 minutes. PdCl2(dppf)-dichloromethane adduct (52.5 mg, 0.064 mmol) was added and the reaction was heated to 100° C. overnight. The cooled reaction mixture was diluted with water and extracted dichloromethane (3×). The organic layer was concentrated under reduced pressure and purified by reverse phase chromatography to yield 2-methyl-2-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]amino}butanenitrile. MS APCI calc'd for C22H22F3N6 [M+H]+ 427. found 427. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=5.3, 1H), 8.44 (s, 1H), 7.85-7.68 (m, 1H), 7.31 (t, J=17.9, 2H), 7.14-6.93 (m, 2H), 6.76 (d, J=9.3, 1H), 2.41 (s, 3H), 2.17-2.03 (m, 2H), 1.62 (s, 3H), 0.93 (t, J=7.3, 3H).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted dichloromethane (3×)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-b8e4ded23ed2400eb64c29261839e611
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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