Dimethylformamide → HCID 60197678, compound

HRID 2408705Notes

Reaction equation

HRID 2408705 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:25])[CH2:9][N:10]2[C:22]3[N:21]=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=3[C:16]3[CH2:15][N:14]([CH3:24])[CH2:13][CH2:12][C:11]2=3)=[CH:4][CH:3]=1.[CH3:26][N:27](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.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>[CH3:23][C:19]1[CH:20]=[N:21][C:22]2[N:10]([CH2:9][CH:8]([C:5]3[CH:4]=[CH:3][C:2]([C:26]#[N:27])=[N:7][CH:6]=3)[OH:25])[C:11]3[CH2:12][CH2:13][N:14]([CH3:24])[CH2:15][C:16]=3[C:17]=2[CH:18]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86677148HCID 86677148, compound

Product 1

HCID 60197678HCID 60197678, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

1-(6-Bromo-pyridin-3-yl)-2-(3,6-dimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-ethanol (2 g, 4.9 mmol) was dissolved in DMF (20 mL), and the mixture was purged with nitrogen. Zinc cyanide (1.16 g, 9.9 mmol) and Pd(PPh3)4 (339 mg, 0.294 mmol) were added, and the mixture heated at 150° C. for 2 h. The reaction was monitored by LCMS. The reaction mixture was allowed to cool at RT, diluted with EtOAc (250 mL) and filtered. The filtrate was washed with water (3×100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude that was purified by reverse phase chromatography to obtain 100 mg of 5-[2-(3,6-dimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-1-hydroxy-ethyl]-pyridine-2-carbonitrile. This was followed by chiral separation. 1H NMR (CDCl3, Free base) δ (ppm): 8.62 (s, 1H), 8.03 (s, 1H), 7.73 (d, 1H), 7.6 (d, 1H), 7.5 (s, 1H), 5.25 (d, 1H), 4.45 (d, 1H), 4.3 (dd, 1H), 3.55 (dd, 2H), 2.8 (m, 1H), 2.7 (m, 2H), 2.5 (s, 3H), 2.45 (s, 3H), 2.4 (m, 1H). Separation by chiral HPLC provided enantiomers II-114a-b.

Workup

  1. customthe mixture was purged with nitrogen
  2. temperatureto cool at RT
  3. filtrationfiltered
  4. washThe filtrate was washed with water (3×100 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto obtain the crude that
  8. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-af14da19019d434d846948d91ccafe89
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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