Cyanogen Bromide → 8-(3-Bromo-4-fluorophenyl)-8-[4-(trifluoromethoxy)phenyl]-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-ylamine

HRID 272662Notes

Reaction equation

HRID 272662 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]([NH2:27])([CH:21]2[NH:26][CH2:25][CH:24]=[CH:23][NH:22]2)[C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[N:28]#[C:29]Br>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2([C:10]3[CH:11]=[CH:12][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[C:21]3=[N:26][CH2:25][CH2:24][CH2:23][N:22]3[C:29]([NH2:28])=[N:27]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 10476Cyanogen BromideHCID 688988571-(3-Bromo-4-fluorophenyl)-1-(tetrahydropyrimidin-2-yl)-1-[4-(trifluoromethoxy)phenyl]methylamine

Product 1

HCID 598378898-(3-Bromo-4-fluorophenyl)-8-[4-(trifluoromethoxy)phenyl]-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-ylamineYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-(3-bromo-4-fluorophenyl)-1-(tetrahydropyrimidin-2-yl)-1-[4-(trifluoromethoxy)phenyl]methylamine (0.85 g, ˜80% purity, ˜1.52 mmol) and cyanogen bromide (0.81 g, 7.62 mmol) in acetonitrile is stirred at room temperature for 45 min, heated at 100° C. in a sealed tube overnight, cooled to room temperature and concentrated. The resultant residue is purified by flash chromatography (silica, 95:5:0.25 methylene chloride/methanol/concentrated ammonium hydroxide as eluent) to afford the title compound as a tan solid, 0.26 g (36% yield), identified by NMR and mass spectral analyses. 1H NMR (300 MHz, CDCl3) δ 7.74 (dd, J=6.7, 2.3 Hz, 1H), 7.49 (dd, J=6.7, 2.1 Hz, 2H), 7.38 (m, 1H), 7.13 (d, J=8.1 Hz, 2H), 7.03 (t, J=8.5 Hz, 1H), 3.58 (m, 4H), 1.86 (m, 2H); ESI MS m/z 471 [C19H15BrF4N4O+H]+.

Workup

  1. temperatureheated at 100° C. in a sealed tube overnight
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. customThe resultant residue is purified by flash chromatography (silica, 95:5:0.25 methylene chloride/methanol/concentrated ammonium hydroxide as eluent)

Sources & evidence

ORD record
ord-5b442fad38ef4ef6b3b103843784b12b
Source dataset
uspto-grants-2008_11
Patent number
US07456186B2

Reaction notes

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