Dimethylformamide → HCID 68897683, compound

HRID 272663Notes

Reaction equation

HRID 272663 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=3)[C:13]3=[N:14][CH2:15][CH2:16][CH2:17][N:12]3[C:11]([NH2:18])=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[F:30][C:31]1[CH:32]=[N:33][CH:34]=C([Sn](CCCC)(CCCC)CCCC)[CH:36]=1.C[N:51](C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=3)[C:13]3=[N:14][CH2:15][CH2:16][CH2:17][N:12]3[C:11]([NH2:18])=[N:10]2)=[CH:3][C:2]=1[N:33]1[CH:32]=[C:31]([F:30])[CH:36]=[N:51][CH2:34]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 468399773-Fluoro-5-(tributylstannyl)pyridineHCID 598378898-(3-Bromo-4-fluorophenyl)-8-[4-(trifluoromethoxy)phenyl]-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-ylamine

Product 1

HCID 68897683HCID 68897683, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
150 °C

Procedure

A mixture of 8-(3-bromo-4-fluorophenyl)-8-[4-(trifluoromethoxy)phenyl]-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-ylamine (0.075 g, 0.159 mmol), 3-fluoro-5-(tributylstannyl)pyridine (0.092 g, 0.239 mmol), and dichlorobis(triphenylphosphine)palladium(II) (0.006 g, 0.008 mmol) in DMF is degassed, heated at 150° C. in a sealed tube for 1.5 h, cooled to room temperature and diluted with ethyl acetate (50 mL) and 5% aqueous LiCl. The reaction mixture is separated. The organic phase is washed with 5% aqueous LiCl, dried over sodium sulfate 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 product as a white solid, 0.043 g (56% yield), mp 94-105° C.; identified by NMR and mass spectral analyses. 1H NMR (300 MHz, CD3OD) 8.56 (d, J=1.3 Hz, 1H), 8.47 (d, J=2.6 Hz, 1H), 7.83 (d, J=9.7 Hz, 1H), 7.54-7.44 (m, 4H), 7.41-7.21 (m, 3H), 3.69 (m, 2H), 3.50 (m, 2H), 1.87 (m, 2H); ESI MS m/z 488 [C24H18F5N5O+H]+;

Workup

  1. customis degassed
  2. temperaturecooled to room temperature
  3. additiondiluted with ethyl acetate (50 mL) and 5% aqueous LiCl
  4. customThe reaction mixture is separated
  5. washThe organic phase is washed with 5% aqueous LiCl
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. 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-b75ce000d35e4e0b8694b0507531ad33
Source dataset
uspto-grants-2008_11
Patent number
US07456186B2

Reaction notes

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