1-Chloroethyl chloroformate → HCID 9797716, compound

HRID 864369Notes

Reaction equation

HRID 864369 reaction equation
ClC(OC(Cl)C)=O.[CH2:8]([N:15]1[CH2:20][CH2:19][C:18](/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:17]([F:29])[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CN(CC1C2[C:37](=[N:38]C=CC=2)[NH:36]C=1)C>ClCCl.C1(C)C=CC=CC=1>[F:29][C:17]1[CH2:16][N:15]([CH2:8][C:9]2[C:10]3[C:37](=[N:38][CH:13]=[CH:12][CH:11]=3)[NH:36][CH:14]=2)[CH2:20][CH2:19][C:18]=1/[CH:21]=[CH:22]/[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 5213051-Chloroethyl chloroformateHCID 53835493-(Dimethylaminomethyl)-7-azaindoleHCID 19418985HCID 19418985, compound

Product 1

HCID 9797716HCID 9797716, compoundYield 51.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (0.048 ml, 0.44 mmol) was added dropwise to a solution of (E)-1-benzyl-3-fluoro-4-(2-phenylethenyl)-1,2,5,6-tetrahydropyridine (0.1002 g, 0.342 mmol) in dichloromethane (2 ml) at -8° C. The mixture was stirred at -8° C. to 0° C. for 1 hour, concentrated in vacuo, the residue redissolved in methanol (5 ml) and heated at reflux for fifteen minutes. The reaction mixture was evaporated and the residue partitioned between saturated aqueous potassium carbonate (25 ml) and dichloromethane (2×25 ml). The organic extracts were washed with brine (25 ml), combined, dried (MgSO4) and concentrated in vacuo. The residue and 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (0.0606 g, 0.346 mmol) were suspended in toluene (5 ml) and the mixture stirred at reflux for 12 hours. The toluene was evaporated and the product purified by flash chromatography, eluting with dichloromethane/methanol/ammonia (120:8:1), to afford the title compound (0.0585 g, 51%). Recrystalisation from methanol gave buff needles, m.p. 218°-221° C. (dec.); δH (DMSO-d6) 2.35 (2H, m, tetrahydropyridinyl CH2), 2.64 (2H, m, tetrahydropyridinyl CH2), 3.16 (2H, br s, tetrahydropyridinyl CH2), 3.80 (2H, s, ArCH2N), 6.52 (1H, d, J 16.4Hz, CH=CHPh), 7.05 (1H, dd, J 7.8, 4.7Hz, 5-H), 7.14 (1H, d, J 16.4Hz, CH=CHPh), 7.23 (1H, m, ArH), 7.32 (2H, m, ArH), 7.42 (1H, s, 2-H), 7.48 (2H, m, ArH), 8.05 (1H, dd, J 7.8, 1.4Hz, 4-H), 8.20 (1H, dd, J 4.7, 1.4Hz, 6-H) and 11.51 (1H, br s, NH); m/z (CI+, NH3) 334 (M+1)+.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe residue redissolved in methanol (5 ml)
  3. temperatureheated
  4. temperatureat reflux for fifteen minutes
  5. customThe reaction mixture was evaporated
  6. customthe residue partitioned between saturated aqueous potassium carbonate (25 ml) and dichloromethane (2×25 ml)
  7. washThe organic extracts were washed with brine (25 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. stirringthe mixture stirred
  11. temperatureat reflux for 12 hours
  12. customThe toluene was evaporated
  13. customthe product purified by flash chromatography
  14. washeluting with dichloromethane/methanol/ammonia (120:8:1)

Sources & evidence

ORD record
ord-991e5b5cabcb439cbeb42d6f29e121db
Source dataset
uspto-grants-1996_10
Patent number
US05563150

Reaction notes

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