Potassium Carbonate → 2-((1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)ethynyl)bicyclo[2.2.1]heptan-2-ol

HRID 1398697Notes

Reaction equation

HRID 1398697 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH3:10])[N:7]([C:11]3[N:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=3)[C:6]=2[CH:18]=1.[C:19]([C:21]1([OH:28])[CH2:26][CH:25]2[CH2:27][CH:22]1[CH2:23][CH2:24]2)#[CH:20].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu]I>[NH2:17][C:13]1[N:14]=[CH:15][N:16]=[C:11]([N:7]2[C:6]3[CH:18]=[C:2]([C:20]#[C:19][C:21]4([OH:28])[CH2:26][CH:25]5[CH2:27][CH:22]4[CH2:23][CH2:24]5)[CH:3]=[CH:4][C:5]=3[N:9]=[C:8]2[CH3:10])[N:12]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 143098132-Ethynylbicyclo(2.2.1)heptan-2-olHCID 681818904-(6-Bromo-2-methyl-benzoimidazol-1-yl)-[1,3,5]triazin-2-ylamine

Product 1

HCID 681817002-((1-(4-amino-1,3,5-triazin-2-yl)-2-methyl-1H-benzo[d]imidazol-6-yl)ethynyl)bicyclo[2.2.1]heptan-2-olYield 8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(6-bromo-2-methyl-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-amine (200 mg, 0.66 mmol) and 2-ethynylbicyclo[2.2.1]heptan-2-ol (85 mg, 1.3 mmol) in DMF (2.5 mL) was treated with palladium(II) acetate (16 mg, 0.07 mmol), DPPP (58 mg, 0.14 mmol), copper(I) iodide (5 mg, 0.04 mmol) and potassium carbonate (180 mg, 1.3 mmol), then the mixture was heated at 120° C. for 40 min under microwave irradiation. After cooling to RT, the reaction mixture was filtered and the filtrate concentrated in vacuo. Purification of the residue by silica gel column chromatography furnished the title compound (18.5 mg, yield 8%): 1H NMR: (400 MHz, MeOD) delta 1.30-1.47 (m, 4H), 1.56-1.67 (m, 1H), 1.92-2.48 (m, 5H), 2.97 (s, 3H), 7.36 (dd, J=1.6, 8.4 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 8.50 (s, 1H), 8.60 (s, 1H); LC-MS: m/z=+361.0 (M+H)+.

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customPurification of the residue by silica gel column chromatography

Sources & evidence

ORD record
ord-ce47143e6b564d6d82021c877fba44c4
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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