1,2-Dichloroethane → N-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenethylthio)-1H-pyrrole-2-carboxamide

HRID 1987924Notes

Reaction equation

HRID 1987924 reaction equation
[CH2:1]([S:9][C:10]1[CH:11]=[C:12]([C:15]([OH:17])=O)[NH:13][CH:14]=1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH2:18][C:19]1[CH:30]=[CH:29][C:22]([O:23][CH2:24][C:25]([CH3:28])([OH:27])[CH3:26])=[C:21]([O:31][CH3:32])[CH:20]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>ClC(Cl)C.CCOC(C)=O>[OH:27][C:25]([CH3:28])([CH3:26])[CH2:24][O:23][C:22]1[CH:29]=[CH:30][C:19]([NH:18][C:15]([C:12]2[NH:13][CH:14]=[C:10]([S:9][CH2:1][CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:11]=2)=[O:17])=[CH:20][C:21]=1[O:31][CH3:32]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 595950521-(4-Amino-2-methoxyphenoxy)-2-methylpropan-2-olHCID 672152014-(phenethylthio)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 67215051N-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenethylthio)-1H-pyrrole-2-carboxamideYield 47.9%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(phenethylthio)-1H-pyrrole-2-carboxylic acid (25.0 mg, 0.101 mmol) and 1-(4-amino-2-methoxyphenoxy)-2-methylpropan-2-ol (21.4 mg, 0.101 mmol) in dichloroethane (0.880 mL) was added EDC (38.8 mg, 0.202 mmol) and HOBT (30.9 mg, 0.202 mmol) and the reaction was allowed to stir at rt for 16 h. The reaction mixture was diluted with EtOAc (15 mL), washed with sat. NaHCO3 (3×20 mL), water, brine, dried over anhydrous Na2SO4, concentrated and purified by preparative HPLC: Phenomenex Luna AXIA 5μ C18 21.2×100 mm, 15 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 5 min hold; 20 mL/min, UV detection at 220 nm, 10.739 min retention time to afford 21.3 mg of the title compound as brown solid: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 6H), 2.85-2.97 (m, 4H), 3.81 (s, 2H), 3.85 (s, 3H), 6.67 (br. s., 1H), 6.88 (d, J=8.8 Hz, 1H), 6.95 (dd, J=8.8, 2.2 Hz, 1H), 7.02 (s, 1H), 7.15-7.23 (m, 3H), 7.24-7.32 (m, 2H), 7.37 (s, 1H), 7.55 (d, J=3.8 Hz, 1H), 9.83 (br. s., 1H);); HPLC a) column: Phenomenex Luna 5μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 3.650 min retention time, (>98%); HPLC b) column: Phenomenex Luna C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 3.660 min retention time; MS (ES) 441 [M+H]+.

Workup

  1. washwashed with sat. NaHCO3 (3×20 mL), water, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated
  4. custompurified by preparative HPLC
  5. customC18 21.2×100 mm, 15 min gradient, 10% MeOH/90% H2O/0.1% TFA
  6. customto 90% MeOH/10% H2O/0.1% TFA, 5 min

Sources & evidence

ORD record
ord-5ca9d9d412104cc2a302ceaf72ecb9f7
Source dataset
uspto-grants-2009_06
Patent number
US07553836B2

Reaction notes

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