1,2-Dichloroethane → HCID 59275466, compound

HRID 555044Notes

Reaction equation

HRID 555044 reaction equation
[CH2:1](Cl)[CH2:2]Cl.[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][C:14]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30](=[O:41])[NH:31][C:32](C5C=CC=CC=5)([CH3:34])[CH3:33])[CH:25]=4)=[C:20]([N+:42]([O-:44])=[O:43])[C:15]=3[C:16]=2[C:17](O)=[O:18])=[CH:8][CH:7]=1.CN.ON1C2N=[CH:54][CH:55]=[CH:56][C:51]=2N=N1.C[CH2:58][N:59](C(C)C)C(C)C>C(Cl)Cl>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[O:13][C:14]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30](=[O:41])[NH:31][C:32]([C:2]5[CH:1]=[CH:51][CH:56]=[CH:55][CH:54]=5)([CH3:34])[CH3:33])[CH:25]=4)=[C:20]([N+:42]([O-:44])=[O:43])[C:15]=3[C:16]=2[C:17]([NH:59][CH3:58])=[O:18])=[CH:10][CH:11]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 67211207HCID 67211207, compound

Product 1

HCID 59275466HCID 59275466, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

EDC (128 mg, 0.668 mmol) was added to a stirring solution of the crude 2-(4-fluorophenyl)-4-nitro-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxylic acid (300 mg, 0.557 mmol), methanamine (306 μL, 0.613 mmol), 1-hydroxy-7-azabenzotriazole (83 mg, 0.613 mmol), DIEA (204 μL, 1.170 mmol) in DCM (5.5 mL) at rt. It was allowed to stir for 3 days. The slurry had gone into solution over that period of time. The mixture was concentrated and purified on silica gel (BIOTAGE®, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the titled compound (220 mg, 95%). 1H NMR (500 MHz, CD3OD) δ ppm 7.90-7.99 (3H, m), 7.85-7.90 (1H, m), 7.82-7.84 (1H, m), 7.49-7.56 (3H, m), 7.45 (2H, d, J=7.32 Hz), 7.27-7.34 (4H, m), 7.19 (1H, t, J=7.32 Hz), 2.87 (3H, s), 1.76 (6H, s). LC-MS retention time: 1.62 min; m/z (MH+): 552. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 μm, Rt=13.60 min, purity=94%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 μm, Rt=12.66 min, purity=96%.

Workup

  1. waitThe slurry had gone into solution over that period of time
  2. concentrationThe mixture was concentrated
  3. custompurified on silica gel (BIOTAGE®, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

Sources & evidence

ORD record
ord-c877c7dd6f09408aa69fe4681fceb2b9
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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