Dimethylformamide → HCID 21880584, compound

HRID 724485Notes

Reaction equation

HRID 724485 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[Cl:30])[N:10]=[C:11]3[C:16](=[O:17])[N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:14]([CH3:23])=[N:13][C:12]=23)=[CH:4][CH:3]=1.[CH3:31][N:32](C=O)C>[C-]#N.[C-]#N.[Zn+2].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>[Cl:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[N:9]1[C:8]([C:5]2[CH:4]=[CH:3][C:2]([C:31]#[N:32])=[CH:7][CH:6]=2)=[C:12]2[N:13]=[C:14]([CH3:23])[N:15]([CH2:18][C:19]([F:20])([F:22])[F:21])[C:16](=[O:17])[C:11]2=[N:10]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 11363997HCID 11363997, compound

Product 1

HCID 21880584HCID 21880584, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
200 °C

Procedure

A mixture of 3-(4-bromophenyl)-2-(2-chlorophenyl)-5-methyl-6-(2,2,2-trifluoroethyl)-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one (4A-9, 109 mg, 0.23 mmol), Zn(CN)2 (29 mg, 0.25 mmol), Pd(PPh3)4 (6.8 mg, 5.9 μmol) in DMF (2.5 ml) was heated in a microwave apparatus (Emrys Optimizer, Personal Chemistry) at 200° C. for 10 minutes. The reaction mixture was quenched with saturated aqueous NaCl, filtered, and extracted with EtOAc (2×). The combined organic extracts were dried (Na2SO4) and concentrated under vacuum. The crude residue was purified on a Chromatotron using 1 mm plates and a solvent gradient of 33% EtOAc/hexanes to 50% EtOAc/hexanes to give the desired product, 4-[2-(2-chlorophenyl)-5-methyl-7-oxo-6-(2,2,2-trifluoroethyl)-6,7-dihydro-2H-pyrazolo[4,3-d]pyrimidin-3-yl]-benzonitrile (5A-1), as an amorphous solid (145 mg): MS (m/z) 444.4 (M+H)+; 1H NMR (400 MHz, CDCl3): δ 7.63–7.53 (m, 5H), 7.52–7.42 (m, 3H), 5.00–4.80 (br m, 2H), 2.66 (s, 3H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaCl
  2. filtrationfiltered
  3. extractionextracted with EtOAc (2×)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customThe crude residue was purified on a Chromatotron

Sources & evidence

ORD record
ord-a1a3dfb05bff44429b5be9f3cdb548b8
Source dataset
uspto-grants-2006_11
Patent number
US07141669B2

Reaction notes

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