Dimethylformamide → HCID 59275239, compound

HRID 555071Notes

Reaction equation

HRID 555071 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:15][C:16]3[CH:25]=[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:29])=[O:28])[C:23]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38](=[O:49])[NH:39][C:40]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)([CH3:42])[CH3:41])[CH:33]=4)=[CH:22][C:17]=3[C:18]=2[C:19]([OH:21])=O)=[CH:10][CH:9]=1.[CH3:50][N:51](C=O)C.CCN(C(C)C)C(C)C.CN>ClCCCl.CCOC(C)=O>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:15][C:16]3[CH:25]=[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:28])=[O:29])[C:23]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38](=[O:49])[NH:39][C:40]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=5)([CH3:41])[CH3:42])[CH:33]=4)=[CH:22][C:17]=3[C:18]=2[C:19]([NH:51][CH3:50])=[O:21])=[CH:10][CH:9]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 59275558HCID 59275558, compound

Product 1

HCID 59275239HCID 59275239, compoundYield 42.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Oxalyl chloride (22 μL, 0.250 mmol) was added to a stirring solution of 2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)benzofuran-3-carboxylic acid (50 mg, 0.083 mmol) in DCE (832 μL) at rt. DMF (3 μL, 0.042 mmol) was added. The mixture was allowed to stir for 30 min, concentrated and diluted with THF. DIEA (59 μL, 0.333 mmol) and methanamine (208 μL, 0.416 mmol, 2M in THF) was added. It was allowed to stir overnight. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (11 mg, 20%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.46-8.56 (1H, m), 8.36 (1H, s), 7.97-8.05 (3H, m), 7.94 (1H, s), 7.86 (1H, d, J=7.78 Hz), 7.59-7.67 (2H, m), 7.53 (1H, t, J=7.65 Hz), 7.35-7.42 (4H, m), 7.29 (2H, t, J=7.78 Hz), 7.17 (1H, t, J=7.28 Hz), 3.06 (3H, s), 3.01 (3H, s), 2.82 (3H, d, J=4.52 Hz), 1.69 (6H, s). LC-MS retention time: 1.51 min; m/z (MH+): 614. 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 mm, Rt=12.89 min, purity=92%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 mm, Rt=12.11 min, purity=91%.

Workup

  1. concentrationconcentrated
  2. additiondiluted with THF
  3. stirringto stir overnight
  4. washwashed
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customwas purified by preparative reverse phase HPLC on a C18 column
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-78af517b2744438e8baaf25594a23eb9
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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