Potassium Carbonate → 2-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(4-fluoro-phenyl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one

HRID 57717Notes

Reaction equation

HRID 57717 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23](I)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.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>[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23]([C:29]4[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=4)[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 1365928032-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-iodo-3H-imidazo[5,1-f][1,2,4]triazin-4-one

Product 1

HCID 1365927472-(1-Benzyl-4-methyl-pyrrolidin-3-yl)-7-(4-fluoro-phenyl)-3H-imidazo[5,1-f][1,2,4]triazin-4-oneYield 86.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of compound 6 (500 mg, 1.14 mmol) and 4-fluorophenylboronic acid (300 mg, 2.14 mmol) in 30 mL of toluene was added K2CO3 (1.0 g, 7.24 mmol). The resulting mixture was degassed by purging with nitrogen for 15 min, before Pd(PPh3)4 (120 mg, 0.10 mmol) was added. The resulting suspension was bubbled with nitrogen for 10 minutes. The reaction mixture was heated to 100° C. for 18 hours and then cooled to room temperature. After removal of the solvent, the residue was purified by chromatography on silica gel column (eluted with PE/EtOAc=5:1 to 1:2) to afford compound 10 (398 mg, 86% yield) as a white solid. LC-MS: m/z 404.31 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 8.34˜8.31 (m, 2H), 7.95 (s, 1H), 7.38 (m, 4H), 7.31 (m, 1H), 7.16 (m, 2H), 3.85 (d, J=12.4 Hz, 1H), 3.63 (d, J=12.4 Hz, 1H), 3.44˜3.40 (m, 1H). 3.05 (d, J=10 Hz, 1H), 2.84 (m, 1H), 2.61 (m, 1H), 2.50˜2.47 (m, 1H), 1.99 (m, 1H), 1.22 (d, J=6.8 Hz, 3H).

Workup

  1. customThe resulting mixture was degassed
  2. additionwas added
  3. customThe resulting suspension was bubbled with nitrogen for 10 minutes
  4. temperaturecooled to room temperature
  5. customAfter removal of the solvent
  6. customthe residue was purified by chromatography on silica gel column (eluted with PE/EtOAc=5:1 to 1:2)

Sources & evidence

ORD record
ord-7c44c0fa72ba4ff7a2cf2cce97f44635
Source dataset
uspto-grants-2016_09
Patent number
US09434733B2

Reaction notes

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