1-Chloroethyl chloroformate → HCID 70346821, compound

HRID 1940559Notes

Reaction equation

HRID 1940559 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([CH2:14][CH3:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=C[CH:3]=1.ClC(OC(Cl)=O)C.[NH:23]1[CH:28]=CCC[CH2:24]1.C[N:30](CC1C2C(=NC=CC=2)NC=1)C>ClCCl.C1(C)C=CC=CC=1>[CH2:14]([C:11]1[CH2:10][CH2:9][N:8]([C:1]2[C:2]3[C:3](=[N:30][CH:5]=[CH:6][CH:7]=3)[N:23]([CH3:28])[CH:24]=2)[CH2:13][CH:12]=1)[CH3:15]

Participants

7

Reactant 4

HCID 5213051-Chloroethyl chloroformateHCID 53835493-(Dimethylaminomethyl)-7-azaindoleHCID 10176084TetrahydropyridineHCID 21462995HCID 21462995, compound

Product 1

HCID 70346821HCID 70346821, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-benzyl-4-ethyl-1,2,3,6-tetrahydropyridine (1.92 g, 9.6 mmol) in anhydrous dichloromethane (50 ml) was cooled to 0° C. and treated with a solution of 1-chloroethylchloroformate (1.34 ml, 12.4 mmol) in anhydrous dichloromethane (10 ml). After stirring at room temperature for one hour, the solvent was evaporated and the residue redissolved in methanol (50 ml). This solution was heated at reflux for one hour. The solvent was evaporated and the residue partitioned between dichloromethane and saturated aqueous potassium carbonate solution. The organic phase was separated, dried (MgSO4) and evaporated in vacuo to afford the crude product (320 mg, 30%) as a colourless oil. A solution of the crude tetrahydropyridine (320 mg, 2.9 mmol) and 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (504 mg, 2.9 mmol) in toluene (10 ml) was stirred at reflux for 16 hours. The solvent was evaporated and the residue chromatographed with 3% methanol in dichloromethane as eluant to afford the title compound (300 mg, 43%) as a colourless solid, m.p. 88°-90° C.; (Found: C, 74.03; H, 7.94; N, 16.97. C15H19N3.0.125H2O requires C, 73.96; H, 7.97; N, 17.25%); δH (DMSO-d6) 0.99 (3H, t, J 7.5 Hz, CH2CH3), 1.97 (2H, q, J 7.5 Hz, CH2CH3), 2.06-2.12 (2H, m, tetrahydropyridinyl CH2), 2.61 (2H, t, J 5.8 Hz, tetrahydropyridinyl CH2), 3.02-3.08 (2H, m, tetrahydropyridinyl CH2), 3.78 (2H, s, NCH2Ar), 5.34-5.40 (1H, m, tetrahydropyridinyl 5-H), 7.08 (1H, dd, J 7.9, 4.8 Hz, 5-H), 7.29 (1H, m, 2-H), 8.06-8.04 (1H, m, 4-H), 8.28-8.32 (1H, m, 6-H), 9.28 (1H, br s, NH). m/z (CI+, NH3) 242 (M+1)+.

Workup

  1. customthe solvent was evaporated
  2. dissolutionthe residue redissolved in methanol (50 ml)
  3. temperatureThis solution was heated
  4. temperatureat reflux for one hour
  5. customThe solvent was evaporated
  6. customthe residue partitioned between dichloromethane and saturated aqueous potassium carbonate solution
  7. customThe organic phase was separated
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customto afford the crude product (320 mg, 30%) as a colourless oil
  11. temperatureat reflux for 16 hours
  12. customThe solvent was evaporated
  13. customthe residue chromatographed with 3% methanol in dichloromethane as eluant

Sources & evidence

ORD record
ord-743cdfaaf30141358d49ed716cd5c9c6
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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