1,2-Dichloroethane → HCID 46940410, compound

HRID 1914834Notes

Reaction equation

HRID 1914834 reaction equation
[CH3:1][C:2]1[CH:36]=[C:5]2[N:6]=[CH:7][C:8]3[CH:13]=[C:12]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:11]([C:20]4[CH:35]=[CH:34][C:23]([CH2:24][N:25]5[CH2:30][CH2:29][CH:28]([C:31](O)=[O:32])[CH2:27][CH2:26]5)=[CH:22][CH:21]=4)=[N:10][C:9]=3[N:4]2[N:3]=1.[CH:37]1[CH:38]=[CH:39][C:40]2N(O)N=[N:43][C:41]=2[CH:42]=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C.NC1C=CC=CC=1>CN(C=O)C.C(Cl)Cl.O>[CH3:1][C:2]1[CH:36]=[C:5]2[N:6]=[CH:7][C:8]3[CH:13]=[C:12]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:11]([C:20]4[CH:35]=[CH:34][C:23]([CH2:24][N:25]5[CH2:26][CH2:27][CH:28]([C:31](=[O:32])[NH:43][C:41]6[CH:42]=[CH:37][CH:38]=[CH:39][CH:40]=6)[CH2:29][CH2:30]5)=[CH:22][CH:21]=4)=[N:10][C:9]=3[N:4]2[N:3]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6115AnilineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 46940151HCID 46940151, compound

Product 1

HCID 46940410HCID 46940410, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Compound (14-1) (20 mg, 0.042 mmol, 1.0 eq), HOBt (11 mg, 0.084 mmol, 2.0 eq), EDC (HCl salt, 12 mg, 0.063 mmol, 1.5 eq) and diisopropylethylamine (22 μL, 0.13 mmol, 3.0 eq) were dissolved in DMF (400 μL, anhydrous) and CH2Cl2 (400 μL, anhydrous). To this solution was added aniline (19 mg, 0.21 mmol, 5.0 eq) and the reaction stirred at room temperature for 16 hours. After that time water was added and the mixture extracted with CHCl3 (×3). The combined organic phases were dried with brine and Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel chromatography by eluting with a gradient of CHCl3 to [CHCl3/MeOH/NH4OH 90:10:1]. The resulting solid was then dissolved in MeOH, added TFA (100 μL), and purified by reverse-phase chromatography (Solvent A H2O/CH3CN/TFA (95:5:0.05), Solvent B CH3CN/H2O/TFA (95:5:0.05)) with a gradient of 5% to 60% B over 5 minutes to give Compound (15-1)

Workup

  1. extractionthe mixture extracted with CHCl3 (×3)
  2. dry with materialThe combined organic phases were dried with brine and Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography
  5. washby eluting with a gradient of CHCl3 to [CHCl3/MeOH/NH4OH 90:10:1]
  6. dissolutionThe resulting solid was then dissolved in MeOH
  7. additionadded TFA (100 μL)
  8. custompurified by reverse-phase chromatography (Solvent A H2O/CH3CN/TFA (95:5:0.05), Solvent B CH3CN/H2O/TFA (95:5:0.05)) with a gradient of 5% to 60% B over 5 minutes

Sources & evidence

ORD record
ord-67d06c60f9494f489adad56e0673ac5d
Source dataset
uspto-grants-2013_12
Patent number
US08614221B2

Reaction notes

Loading…