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

HRID 1095591Notes

Reaction equation

HRID 1095591 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1I.[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>[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[CH:7]=[CH:6][N:5]=[CH:4][C:3]=3[C:19]=2[CH3:20])([OH:17])[CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 15165104-Amino-3-iodopyridineHCID 574751584-(Dimethylamino)-4-phenyl-1-(prop-1-ynyl)cyclohexanol

Product 1

HCID 574751734-dimethylamino-1-(3-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-4-phenylcyclohexanolYield 21.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

4-Amino-3-iodopyridine (2,331 mg, 10.60 mmol), 4-(dimethylamino)-4-phenyl-1-(prop-1-ynyl)cyclohexanol (3,000 mg, 11.66 mmol, diastereomer mixture), lithium chloride (472 mg, 11.13 mmol) and sodium carbonate (3,369 mg, 31.79 mmol) were combined in dimethylformamide (absolute, 45 ml) in an argon atmosphere. The catalyst ([Pd(dppf)Cl2×CH2Cl2], 865 mg, 1.06 mmol) was then added. The red solution was heated at 100° C. (oil bath temperature) for 4 h. The black reaction mixture was cooled to room temperature and water (50 ml; stirring for 10 min), methylene chloride (50 ml) and saturated sodium chloride solution (100 ml for better phase separation) were added in succession. The phases were separated. The mixture was filtered over kieselguhr beforehand. The aqueous phase was extracted with methylene chloride (3×30 ml). The combined organic phases were washed with saturated sodium chloride solution (3×20 ml), dried with sodium sulfate and filtered and the volatile constituents were then removed completely in vacuo. The residue was absorbed on silica gel and separated by chromatography (silica gel [200 g]; chloroform/ethanol [9:1 1,000 ml, 5:1, 500 ml, 3:1, 500 ml, 1:1, 500 ml and 1:3, 500 ml]). 800 mg of 4-dimethylamino-1-(3-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-4-phenylcyclohexanol (non-polar diastereoisomer) were isolated as a colourless solid and 765 mg of the polar diastereoisomer were isolated as a colourless solid.

Workup

  1. customThe black reaction mixture
  2. temperaturewas cooled to room temperature
  3. customwater (50 ml; stirring for 10 min), methylene chloride (50 ml) and saturated sodium chloride solution (100 ml for better phase separation)
  4. additionwere added in succession
  5. customThe phases were separated
  6. filtrationThe mixture was filtered over kieselguhr beforehand
  7. extractionThe aqueous phase was extracted with methylene chloride (3×30 ml)
  8. washThe combined organic phases were washed with saturated sodium chloride solution (3×20 ml)
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. customthe volatile constituents were then removed completely in vacuo
  12. customThe residue was absorbed on silica gel
  13. customseparated by chromatography (silica gel [200 g]; chloroform/ethanol [9:1 1,000 ml, 5:1, 500 ml, 3:1, 500 ml, 1:1, 500 ml and 1:3, 500 ml])

Sources & evidence

ORD record
ord-7913f8f85e334f5890e4b95a90434cf0
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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