Tert-Butylamine → HCID 59275546, compound

HRID 555072Notes

Reaction equation

HRID 555072 reaction equation
[C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Si]([O:46][CH2:47][CH2:48][N:49]([C:54]1[C:73]([C:74]2[CH:75]=[C:76]([CH:80]=[CH:81][CH:82]=2)[C:77](O)=[O:78])=[CH:72][C:57]2[C:58]([C:68](=[O:71])[NH:69][CH3:70])=[C:59]([C:61]3[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=3)[O:60][C:56]=2[CH:55]=1)[S:50]([CH3:53])(=[O:52])=[O:51])(C(C)(C)C)(C)C>CN(C=O)C.CCOC(C)=O>[C:1]([NH:5][C:77]([C:76]1[CH:75]=[C:74]([C:73]2[C:54]([N:49]([CH2:48][CH2:47][OH:46])[S:50]([CH3:53])(=[O:51])=[O:52])=[CH:55][C:56]3[O:60][C:59]([C:61]4[CH:66]=[CH:65][C:64]([F:67])=[CH:63][CH:62]=4)=[C:58]([C:68]([NH:69][CH3:70])=[O:71])[C:57]=3[CH:72]=2)[CH:82]=[CH:81][CH:80]=1)=[O:78])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67211167HCID 67211167, compound

Product 1

HCID 59275546HCID 59275546, compoundYield 24.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butylamine (21 μL, 0.195 mmol) was added to a stirring solution of HATU (45 mg, 0.117 mmol), DIEA (41 μL, 0.234 mmol), and 3-(6-(N-(2-(tert-butyldimethylsilyloxy)ethyl)methylsulfonamido)-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (50 mg, 0.078 mmol) in DMF (780 μL) at rt. It was allowed to stir for 1 hour. 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, 23%). 1H NMR (500 MHz, CD3OD) δ ppm 8.04 (1H, br. s.), 7.94-8.02 (2H, m), 7.77-7.86 (2H, m), 7.66-7.73 (2H, m), 7.49-7.59 (2H, m), 7.24-7.34 (2H, m), 3.56-3.66 (1H, m), 3.35-3.43 (2H, m), 3.27 (3H, s), 2.94 (3H, s), 2.78-2.87 (1H, m), 1.47 (9H, s). LC-MS retention time: 1.57 min; m/z (MH+): 582. 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=10.88 min, purity=97%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 mm, Rt=10.27 min, purity=96%.

Workup

  1. washwashed
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customwas purified by preparative reverse phase HPLC on a C18 column
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-254e8bd9d3724035a1dee9e89bd097c0
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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