1,2-Dichloroethane → 4-({Acetyl[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-N-[2-amino-5-(2-thienyl)phenyl]benzamide

HRID 509306Notes

Reaction equation

HRID 509306 reaction equation
[C:1]([N:4]([CH2:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1)[CH2:5][C:6]1[N:7]=[N:8][N:9]([CH3:11])[CH:10]=1)(=[O:3])[CH3:2].CC([N:26]([C:30]1[CH:35]=[CH:34][C:33]([C:36]2[S:37][CH:38]=[CH:39][CH:40]=2)=[CH:32][C:31]=1[NH:41]C(C1C=CC(CCl)=CC=1)=O)C(=O)[O-])(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(Cl)Cl.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O.CN(C=O)C>[C:1]([N:4]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]([NH:41][C:31]2[CH:32]=[C:33]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)[CH:34]=[CH:35][C:30]=2[NH2:26])=[O:19])=[CH:20][CH:21]=1)[CH2:5][C:6]1[N:7]=[N:8][N:9]([CH3:11])[CH:10]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 596272824-({Acetyl[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)benzoic acidHCID 866493181,1-Dimethylethyl[2-({[4-(chloromethyl)phenyl]carbonyl}amino)-4-(2-thienyl)phenyl]carbamate

Product 1

HCID 596272614-({Acetyl[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-N-[2-amino-5-(2-thienyl)phenyl]benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

4-({Acetyl[(1-methyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)benzoic acid (17.7 mg, 0.061 mmol), 1,1-dimethylethyl[2-({[4-(chloromethyl)phenyl]carbonyl}amino)-4-(2-thienyl)phenyl]carbamate (22 mg, 0.074 mmol), HOBT (11 mg, 0.074 mmol) and EDC (12 mg, 0.074 mmol) were taken into DMF (409 ul) and stirred at 60° C. overnight. The reaction was diluted with EtOAc and washed with ½ saturated NaHCO3 3×, brine, dried (MgSO4) and concentrated to afford a residue taken into ca 1 mL DCM:TFA (2:1) and stirred for 2 h. This solution was concentrated and purified via HPLC (20-100% MeCN in water with 0.025% TFA) to afford fractions poured into sat. aq. NaHCO3 and extracted with EtOAc 2×. The combined organic layers were washed with brine, dried (MgSO4) and concentrated to afford the requisite material as a dark tan solid. 1H NMR (d6-DMSO, 600 MHz, 90° C.) δ 9.46 (br s, 1H), 8.00-7.90 (m, 3H), 7.50 (d, J=2.1 Hz, 1H), 7.32 (d, J=8.2 Hz, 2H), 7.29 (dd, J=5.3, 1.2 Hz, 1H), 7.24 (dd, J=8.5, 2.3 Hz, 1H), 7.17 (dd, J=3.5, 1.2 Hz, 1H), 7.01 (dd, J=5.0, 3.5 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 4.94 (br s, 2H), 4.66-4.54 (m, 3H), 4.50 (s, 2H), 3.98 (s, 2H), 2.24-2.00 (m, 3H). MS: cal'd 461 (MH+), exp 461 (MH+).

Workup

  1. washwashed with ½ saturated NaHCO3 3×, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customto afford a residue
  5. stirringstirred for 2 h
  6. concentrationThis solution was concentrated
  7. custompurified via HPLC (20-100% MeCN in water with 0.025% TFA)
  8. customto afford fractions
  9. extractionextracted with EtOAc 2×
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-40b85594fca14b94bae6c0fa1279b70f
Source dataset
uspto-grants-2015_08
Patent number
US09096559B2

Reaction notes

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