Dimethylformamide → HCID 10177273, compound

HRID 2416676Notes

Reaction equation

HRID 2416676 reaction equation
Br[C:2]1[CH:11]=[N:10][C:9]2[NH:8][C:7]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:6]=3[C:5]([C:23]([F:26])([F:25])[F:24])([CH2:18][O:19][CH:20]([CH3:22])[CH3:21])[C:4]=2[CH:3]=1.CCOC(C)=O.CCCCCC.[CH3:39][N:40](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>[C:39]([C:2]1[CH:11]=[N:10][C:9]2[NH:8][C:7]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:6]=3[C:5]([C:23]([F:26])([F:24])[F:25])([CH2:18][O:19][CH:20]([CH3:21])[CH3:22])[C:4]=2[CH:3]=1)#[N:40]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 10113225HCID 10113225, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 10177273HCID 10177273, compoundYield 60%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A degassed mix of 3-bromo-7-cyano-5-trifluoromethyl-5-isopropoxymethyl-5,10-dihydrobenzo[b][1,8]naphthyridine (15) (73 mg, 0.171 mmol), Zn(CN)2 (20 mg, 0.171 mmol) and Pd(PPh3)4 (10 mg, 0.00855 mmol) in anhydrous DMF (2 mL) was heated at 100° C. for 16 h 30 min. The reaction mixture was cooled to room temperature, quenched 2 N NH4OH (20 mL), and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Flash chromatography (20%-30% EtOAc-Hexane) provided 17 (38 mg, 60% yield) as a white solid: m.p. 226-227° C.; low resolution mass spectrum (ESI) m/z 371.2 [(M−H)— calcd for C19H14F3N4O: 371.11].

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched 2 N NH4OH (20 mL)
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a88c7b8abde4490c9f663cd2df5df804
Source dataset
uspto-grants-2004_11
Patent number
US06825210B2

Reaction notes

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