1,2-Dichloroethane → HCID 178497907, compound

HRID 1992789Notes

Reaction equation

HRID 1992789 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:28]=[CH:27][C:8]([CH2:9][N:10]2[C:14]([C:15](O)=[O:16])=[CH:13][C:12]([C:18]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[C:20]([F:26])[CH:19]=3)=[N:11]2)=[CH:7][CH:6]=1)=[O:4].[C:29]([CH:33]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]1)([CH3:32])([CH3:31])[CH3:30].C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.C(OCC)(=O)C>[C:29]([C@H:33]1[CH2:34][CH2:35][C@H:36]([NH:39][C:15]([C:14]2[N:10]([CH2:9][C:8]3[CH:27]=[CH:28][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[N:11]=[C:12]([C:18]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[C:20]([F:26])[CH:19]=3)[CH:13]=2)=[O:16])[CH2:37][CH2:38]1)([CH3:32])([CH3:30])[CH3:31]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 793964-tert-ButylcyclohexylamineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 68427678HCID 68427678, compound

Product 1

HCID 178497907HCID 178497907, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the intermediate from step D (0.39 g, 1.0 mmol) in DMF (2 mL) was added 4-tert-butyl cyclohexylamine (268 μL, 1.5 mmol), HOAt (0.2 g, 1.5 mmol), DIEA (0.52 mL, 3.0 mmol) and EDC (0.29 g, 1.5 mmol). The resulting solution was stirred at room temperature for 48 hours. The reaction was diluted with ethyl acetate and washed with IN HCl, saturated NaHCO3, and saturated NaCl. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified on Biotage Quad 3 system using 30% ethyl acetate-hexanes. The trans and cis isomers were obtained in a 3:1 ratio. Isomer A (trans isomer): 1H NMR (CDCl3, 500 MHz): 8.02 (d, J=8.4 Hz, 2H), 7.46 (dd, J=6.7, 7.9 Hz, 2H), 7.41 (d, J=8.2Hz, 2H), 6.75 (s, 1H), 5.86 (s, 2H), 5.83 (d, J=8.2 Hz, 1H), 3.93 (s, 3H), 3.8 (m, 1H), 2.11 (bm, 2H), 1.18 (bm, 2H), 1.2-1.0 (m, 3H), 0.91 (s, 9H). LC-MS: 3.07 min; (M+H)=528.2. Isomer B (cis isomer): 1H NMR (CDCl3, 500 MHz): 8.01 (d, J=8.0 Hz, 2H), 7.48 (t, J=6.6 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 6.73 (s, 1H), 6.08 (d, J=7.1 Hz, 1H), 5.84 (s, 2H), 4.23 (m, 1H), 3.92 (s, 3H), 1.94 (d, J=14.2 Hz, 2H), 1.71 (d, J=11.2 Hz, 2H), 1.61 (m, 211), 1.1 (m, 2H), 0.89 (s, 9H). LC-MS: 3.07 min; (M+H)=528.2.

Workup

  1. washwashed with IN HCl, saturated NaHCO3, and saturated NaCl
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on Biotage Quad 3 system
  6. customThe trans and cis isomers were obtained in a 3:1 ratio
  7. custom3.07 min
  8. custom3.07 min

Sources & evidence

ORD record
ord-d5d3b4ed6eff409f96d2dad2bbb1d769
Source dataset
uspto-grants-2010_01
Patent number
US07649009B2

Reaction notes

Loading…