Dimethylacetamide → HCID 71184873, compound

HRID 1629968Notes

Reaction equation

HRID 1629968 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[O:14])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C[C:23]([N:25](C)C)=O>[C-]#N.[C-]#N.[Zn+2].[Zn].CC(P(C(C)(C)C)C(C)(C)C)(C)C.CC(P(C(C)(C)C)C(C)(C)C)(C)C.[Pd]>[F:21][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=1)[C:13]([N:10]1[CH2:11][CH2:12][C:8]([C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[C:23]#[N:25])=[N:9]1)=[O:14]

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 71185098HCID 71185098, compound

Product 1

HCID 71184873HCID 71184873, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2734558Bis(tri-tert-butylphosphine)palladium(0)Catalyst

Conditions

Temperature
80 °C

Procedure

A scintillation vial equipped with a stir bar was charged with [3-(3-bromo-phenyl)-4,5-dihydro-pyrazol-1-yl]-(3-fluoro-phenyl)-methanone (347 mg, 1.0 mmol), Zn(CN)2 (234 mg, 2.0 mmol), Zn dust (65 mg, 1.0 mmol) and DMA (10 mL). The mixture was degassed and then Pd(t-Bu3P)2 (51 mg, 0.1 mmol) was added. The mixture was heated at 80° C. for 4 h. LC-MS showed consumption of SM. The material was filtered through a pad of Fluorosil and the solvent was evaporated under reduced pressure. It was purified by chromatography using a 12 g silica cartridge eluting with heptane-EtOAc, gradient 30 to 100% EtOAc. Amount obtained: 225 mg, 0.76 mmol, 76% yield. LC-MS (ESI) m/e 294 (M+H). 1H NMR (CHLOROFORM-d) δ: 7.92-7.97 (m, 2H), 7.76 (d, J=7.8 Hz, 1H), 7.66-7.74 (m, 2H), 7.52-7.59 (m, 1H), 7.45 (td, J=8.0, 5.8 Hz, 1H), 7.20-7.30 (m, 1H), 4.32 (t, J=10.1 Hz, 2H), 3.26-3.34 (m, 2H). Step 2

Workup

  1. customA scintillation vial equipped with a stir bar
  2. customThe mixture was degassed
  3. customconsumption of SM
  4. filtrationThe material was filtered through a pad of Fluorosil
  5. customthe solvent was evaporated under reduced pressure
  6. customIt was purified by chromatography
  7. washeluting with heptane-EtOAc, gradient 30 to 100% EtOAc
  8. customAmount obtained

Sources & evidence

ORD record
ord-c5fdb99526dc4ac180fe6daab42cc056
Source dataset
uspto-grants-2014_07
Patent number
US08791114B2

Reaction notes

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