Potassium Phosphate, Tribasic → 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842796Notes

Reaction equation

HRID 1842796 reaction equation
[CH3:1][N:2]1[CH2:7][CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH2:4][CH2:3]1.Br[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([NH:26][C:27]2[N:32]=[C:31]([C:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[N:35]([CH3:42])[CH:34]=3)[CH:30]=[CH:29][N:28]=2)=[CH:20][C:19]=1[NH2:43].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH3:25][O:24][C:22]1[CH:23]=[C:18]([C:5]2[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=2)[C:19]([NH2:43])=[CH:20][C:21]=1[NH:26][C:27]1[N:32]=[C:31]([C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]([CH3:42])[CH:34]=2)[CH:30]=[CH:29][N:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 207733711-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridineHCID 866773474-bromo-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine2×

Product 1

HCID 866773014-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1,1 Bis(di-tert-butylphosphino)ferrocene palladium dichloride (16.74 mg, 0.03 mmol) was added to a solution containing 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (139 mg, 0.62 mmol), 4-bromo-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine (Intermediate 144, 220 mg, 0.52 mmol), and K3PO4 (220 mg, 1.04 mmol) in 1,4-dioxane (6 mL) and water (1.5 mL, degassed for 20 minutes prior to use). The mixture was heated at 100° C. for 1 h and then concentrated in vacuo. The resulting residue was dissolved in EtOAc. This solution was washed with water (×3), brine, and was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (191 mg, 84%) as a tan solid after trituration with diethyl ether; 1H NMR: 2.31 (3H, s), 2.37-2.43 (2H, m), 2.61 (2H, t), 3.01-3.04 (2H, m), 3.76 (3H, s), 3.89 (3H, s), 4.37 (2H, br s), 5.70-5.73 (1H, m), 6.63 (1H, s), 7.18-7.22 (2H, m), 7.25-7.29 (1H, m), 7.54 (1H, d), 7.63 (1H, s), 7.81 (1H, s), 8.31 (1H, d), 8.34 (1H, s), 8.46 (1H, d); m/z: ES+ MH+ 441.57.

Workup

  1. customdegassed for 20 minutes
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in EtOAc
  4. washThis solution was washed with water (×3), brine
  5. dry with materialwas then dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by FCC
  8. washeluting with 0-10% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-d0b738c4beb54a81ac6b22ac1b827809
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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