1,2-Dichloroethane → HCID 25014186, compound

HRID 1013475Notes

Reaction equation

HRID 1013475 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][N:11]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[NH2:19][C:20]1[CH:25]=[C:24]([C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)[CH:23]=[CH:22][C:21]=1[NH:31]C(=O)OC(C)(C)C.C(Cl)CCl.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O.C(Cl)Cl.CN(C=O)C>[NH2:31][C:21]1[CH:22]=[CH:23][C:24]([C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)=[CH:25][C:20]=1[NH:19][C:14]([C:13]1[CH:17]=[CH:18][C:10]([CH2:9][P:4](=[O:5])([O:3][CH2:1][CH3:2])[O:6][CH2:7][CH3:8])=[N:11][CH:12]=1)=[O:16]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 57926019HCID 57926019, compound

Product 1

HCID 25014186HCID 25014186, compoundYield 43.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-[(Diethoxyphosphoryl)methyl]nicotinic acid (55.5 mg, 0.188 mmol), tert-butyl [2-amino-4-(2-thienyl)phenyl]carbamate (65.5 mg, 0.226 mmol) HOBT (30.5 mg, 0.226 mmol), and EDC (43.3 mg, 0.226 mmol) was taken into DMF (1.32 mL) and stirred for 3 days. The mixture was diluted with EtOAc and washed with 50% saturated aqueous NaHCO3 3×, brine, dried (MgSO4) and concentrated to afford a residue taken into DCM (2 mL) and TFA (1 mL) and stirred for 1 h. This mixture was concentrated via rotovap, dissolved in minimum MeOH and purified via HPLC (10-100% MeCN in water with 0.025% TFA) to afford fractions poured into saturated aqueous NaHCO3 and extracted with EtOAc 2×. The combined organic layers were washed with brine, dried (MgSO4) and concentrated to afford 36.5 mg of the requisite product as a light yellow solid. 1H NMR (DMSO-d6, 600 MHz) δ 9.84 (s, 1H), 9.04 (s, 1H), 8.26 (dd, J=7.9, 2.0 Hz, 1H), 7.47 (dd, J=8.2, 1.8 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.33 (dd, J=5.0, 0.9 Hz, 1H), 7.28 (dd, J=8.8, 2.3 Hz, 1H), 7.22 (dd, J=3.5, 1.2 Hz, 1H), 7.2 (dd, J=5.0, 3.5 Hz, 1H), 6.78 (d, J=8.2 Hz, 1H), 5.22 (s, 2H), 3.95 (dt, J=7.3, 7.3 Hz, 4H), 3.53 (d, J=22.3 Hz, 2H), 1.19 Hz (t, J=7.0 Hz, 3H). MS: cal'd 446 (MH+), exp 446 (MH+).

Workup

  1. washwashed with 50% saturated aqueous NaHCO3 3×, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customto afford a residue
  5. stirringstirred for 1 h
  6. concentrationThis mixture was concentrated via rotovap
  7. dissolutiondissolved in minimum MeOH
  8. custompurified via HPLC (10-100% MeCN in water with 0.025% TFA)
  9. customto afford fractions
  10. extractionextracted with EtOAc 2×
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-7abfee2e7b4e4ea4800feea604dbd2b1
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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