Tert-Butylamine → 5-[3-(tert-butylcarbamoyl)phenyl]-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide

HRID 1671925Notes

Reaction equation

HRID 1671925 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:18][C:19]3[CH:29]=[CH:28][C:27]([C:30]4[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=4)[C:33](O)=[O:34])=[CH:26][C:20]=3[C:21]=2[C:22](=[O:25])[NH:23][CH3:24])=[CH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:63]([NH2:67])([CH3:66])([CH3:65])[CH3:64]>CN(C=O)C.CC#N>[C:63]([NH:67][C:33]([C:32]1[CH:31]=[C:30]([C:27]2[CH:28]=[CH:29][C:19]3[O:18][C:17]([C:14]4[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=4)=[C:21]([C:22]([NH:23][CH3:24])=[O:25])[C:20]=3[CH:26]=2)[CH:38]=[CH:37][CH:36]=1)=[O:34])([CH3:66])([CH3:65])[CH3:64]

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 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

Product 1

HCID 534686535-[3-(tert-butylcarbamoyl)phenyl]-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamideYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

DIEA (50 μL, 0.29 mmol) was added to a suspension of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (50 mg, 0.13 mmol) and HATU (60 mg, 0.16 mmol) in DMF (0.5 mL). The solids dissolved over 5 min, at which point tert-butylamine (20 μL, 0.19 mmol) was added. The solution was stirred at r.t. for 1 h, then diluted with CH3CN (1 mL), filtered, purified by prep HPLC, concentrated, and dried in a vacuum oven over the weekend at 40° C. to give the title compound (39 mg, 69% yield) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.53 (q, J=4.37 Hz, 1H) 8.08 (s, 1H) 8.01 (dd, J=8.24, 5.80 Hz, 2H) 7.92 (d, J=7.93 Hz, 2H) 7.84 (d, J=7.63 Hz, 1H) 7.77-7.82 (m, 2H) 7.73-7.77 (m, 1H) 7.55 (t, J=7.63 Hz, 1H) 7.40 (t, J=8.85 Hz, 2H) 2.87 (d, J=4.58 Hz, 3H) 1.42 (s, 9H). 13C NMR (125 MHz, DMSO-d6) δ ppm 166.20 (s) 163.22 (s) 162.66 (d, J=246 Hz) 152.56 (s) 152.52 (s) 140.06 (s) 136.53 (s) 135.76 (s) 129.38 (d, J=12 Hz) 129.36 (s) 128.70 (s) 127.86 (s) 126.27 (s) 125.86 (s) 125.70 (d, J=2.5 Hz) 124.83 (s) 118.90 (s) 115.93 (d, J=20 Hz) 113.88 (s) 111.60 (s) 50.85 (s) 28.60 (s) 26.19 (s). LC/MS method: solvent A=5% CH3CN/95% H2O/10 mM NH4OAc, solvent B=95% CH3CN/5% H2O/10 mM NH4OAc, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=5 ml/min, column. XBridge C18 5 μm 4.6×50 mm; HPLC Rt=1.57, (ES−) m/z (M−)=443. Analytical 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, 3.5 μm 4.6×150 mm, Rt=11.71 min, purity=100%; column: Waters Xbridge Phenyl column 3.5 μm 4.6×150 mm, Rt=9.53 min, purity=100%.

Workup

  1. additionwas added
  2. filtrationfiltered
  3. custompurified by prep HPLC
  4. concentrationconcentrated
  5. customdried in a vacuum oven over the weekend at 40° C.

Sources & evidence

ORD record
ord-fc05f95c1c2d453dae35b8049f3a59c9
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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