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

HRID 2420730

Reaction equation

HRID 2420730 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, 6 H), 2.85-2.97 (m, 4 H), 3.81 (s, 2 H), 3.85 (s, 3 H), 6.67 (br. s, 1 H), 6.88 (d, J=8.8 Hz, 1 H), 6.95 (dd, J=8.8, 2.2 Hz, 1 H), 7.02 (s, 1 H), 7.15-7.23 (m, 3 H), 7.24-7.32 (m, 2 H), 7.37 (s, 1 H), 7.55 (d, J=3.8 Hz, 1 H), 9.83 (br. s, 1 H); 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-7c2995b462d7457a90a7f9bcd095c08b
Source dataset
uspto-grants-2011_06
Patent number
US07956049B2

Linked notes

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