Sodium Carbonate → 4-Dimethylamino-1-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-phenylcyclohexanol

HRID 1095554Notes

Reaction equation

HRID 1095554 reaction equation
[NH2:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:9][N:10]([CH3:27])[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH2:15][C:14]([C:18]#[C:19][CH3:20])([OH:17])[CH2:13][CH2:12]1.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH3:27][N:10]([CH3:9])[C:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH2:15][C:14]([C:18]2[NH:1][C:2]3=[N:3][CH:4]=[CH:5][CH:6]=[C:7]3[C:19]=2[CH3:20])([OH:17])[CH2:13][CH2:12]1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27631512-Amino-3-iodopyridine2×HCID 574751584-(Dimethylamino)-4-phenyl-1-(prop-1-ynyl)cyclohexanol

Product 1

HCID 574751594-Dimethylamino-1-(3-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-phenylcyclohexanol

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
79 °C

Procedure

2-Amino-3-iodopyridine (3,108 mg, 14.13 mmol), 4-(dimethylamino)-4-phenyl-1-(prop-1-ynyl)cyclohexanol (4,000 mg, 15.54 mmol), lithium chloride (630 mg, 14.83 mmol) and sodium carbonate (4.49 g, 42.38 mmol) were combined in dimethylformamide (absolute, 60 ml) in an argon atmosphere. The catalyst ([Pd(dppf)Cl2×CH2Cl2], 1,154 mg, 1.41 mmol) was then added. The red solution was heated at 79° C. (oil bath temperature) for 5 h. To bring the reaction to completion, a further 0.3 equivalent of 2-amino-3-iodopyridine (932 mg, 4.24 mmol) and 0.05 equivalent of catalyst (577 mg, 0.71 mmol) were added. Thereafter, the mixture was stirred at 99° C. (oil bath temperature) for a further 2 h. The black reaction mixture was cooled to room temperature and water (50 ml; stirring for 10 min) and methylene chloride (50 ml) were added in succession. The phases were separated (the mixture was filtered over kieselguhr) and the aqueous phase was extracted with methylene chloride (3×20 ml). The combined organic phases were washed with saturated NaCl solution (3×20 ml) and dried over sodium sulfate. After filtration, the volatile constituents were removed completely in vacuo. The residue was absorbed on kieselguhr and separated by chromatography (silica gel [200 g]; chloroform/ethanol [9:1 1,000 ml]). 1,200 mg (3.43 mmol; 22% of the non-polar diastereomer were isolated as a colourless solid.

Workup

  1. customthe reaction to completion
  2. customThe black reaction mixture
  3. temperaturewas cooled to room temperature
  4. customThe phases were separated (the mixture
  5. filtrationwas filtered over kieselguhr) and the aqueous phase
  6. extractionwas extracted with methylene chloride (3×20 ml)
  7. washThe combined organic phases were washed with saturated NaCl solution (3×20 ml)
  8. dry with materialdried over sodium sulfate
  9. filtrationAfter filtration
  10. customthe volatile constituents were removed completely in vacuo
  11. customThe residue was absorbed on kieselguhr
  12. customseparated by chromatography (silica gel [200 g]; chloroform/ethanol [9:1 1,000 ml])
  13. custom22% of the non-polar diastereomer were isolated as a colourless solid

Sources & evidence

ORD record
ord-dc0a07f729714838a71cb04b4e193a41
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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