N-methyl-2-pyrrolidone → HCID 10268983, compound

HRID 2416677Notes

Reaction equation

HRID 2416677 reaction equation
Cl[C:2]1[CH:24]=[CH:23][C:5]2[NH:6][C:7]3[N:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]([CH2:18][O:19][CH:20]([CH3:22])[CH3:21])([C:14]([F:17])([F:16])[CH3:15])[C:4]=2[CH:3]=1.CCOC(C)=O.CCCCCC.[CH3:37][N:38]1C(=O)CCC1>CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.[Zn]>[C:37]([C:2]1[CH:24]=[CH:23][C:5]2[NH:6][C:7]3[N:8]=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]([CH2:18][O:19][CH:20]([CH3:22])[CH3:21])([C:14]([F:17])([F:16])[CH3:15])[C:4]=2[CH:3]=1)#[N:38]

Participants

8

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 21226206Ethyl acetate hexaneHCID 22633359HCID 22633359, compound

Product 1

HCID 10268983HCID 10268983, compoundYield 90%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

A degassed mix of 7-chloro-5-isopropoxymethyl-5-(1,1-difluoroethyl)-5,10-dihydrobenzo[b][1,8]naphthyridine (21)(2.501 g, 7.089 mmol), Zn(CN)2 (849 mg, 7.089 mmol), Pd[P(t-Bu)3]2 (1.479 g, 2.836 mmol) and Zinc powder (556 mg, 8.507 mmol) in anhydrous NMP (20 mL) was heated at 170° C. for 22 h 30 min. The reaction mixture was cooled to room temperature, diluted with EtOAc, filtered through a pad of Celite and washed with EtOAc. The filtrate was washed with 2 N NH4OH (120 mL) and brine, dried over MgSO4, filtered and concentrated in vacuo. Flash chromatography (30%-50% EtOAc-Hexane) provided 22 (2.184 g, 90% yield) as a yellow solid: m.p. 134-135° C.; low resolution mass spectrum (ESI) m/z 344.3 [(M+H)+ calcd for C19H20F2N3O: 344.16].

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a pad of Celite
  3. washwashed with EtOAc
  4. washThe filtrate was washed with 2 N NH4OH (120 mL) and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-502f0ca260c34740a2a66aaa7e302adc
Source dataset
uspto-grants-2004_11
Patent number
US06825210B2

Reaction notes

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