Dimethylformamide → HCID 68284016, compound

HRID 2408623Notes

Reaction equation

HRID 2408623 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:25])[CH2:9][N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:4][CH:3]=1.[CH3:26][N:27](C=O)C>CCOC(C)=O.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-]#N.[Zn+2].[C-]#N>[CH3:24][N:21]1[CH2:22][CH2:23][C:11]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:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]=2[CH2:20]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86677140HCID 86677140, compound

Product 1

HCID 68284016HCID 68284016, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
150 °C

Procedure

To a degassed solution of 1-(6-bromo-pyridin-3-yl)-2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanol (1 g, 2.5 mmol) in DMF (10 mL) were added Pd(PPh3)4 (0.173 g, 0.15 mmol) and zinc cyanide (585 mg, 5.0 mmol) and the reaction mixture was stirred at 150° C. for 2 h. The reaction mixture was cooled to 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. The residue was purified by reverse phase HPLC to yield 5-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-hydroxy-ethyl]-pyridine-2-carbonitrile (350 mg). 1H NMR (CDCl3, freebase) δ (ppm): 8.55 (s, 1H), 7.38 (d, 1H), 7.23 (d, 1H), 6.93 (s, 1H), 6.81 (s 1H), 6.74 (s, 1H), 4.96 (m, 1H), 4.11 (dd, 2H), 3.29 (dd, 2H), 2.95 (m, 1H), 2.88 (m 1H), 2.86 (m, 2H), 2.5 (s, 6H). Separation by chiral HPLC provided enantiomers 140a and 140b.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with water (3×100 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-91838bf39dec46858de9ccb9fe333d13
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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