Cumylamine → 2-(4-fluorophenyl)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)-1H-indole-3-carboxamide

HRID 219339Notes

Reaction equation

HRID 219339 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]3[C:15]([C:16]=2[C:17](=[O:20])[NH:18][CH3:19])=[CH:14][C:13]([C:21]2[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=2)[C:24]([OH:26])=O)=[CH:12][CH:11]=3)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:39]([NH2:48])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([CH3:41])[CH3:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCCl.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10]3[C:15]([C:16]=2[C:17]([NH:18][CH3:19])=[O:20])=[CH:14][C:13]([C:21]2[CH:29]=[CH:28][CH:27]=[C:23]([C:24](=[O:26])[NH:48][C:39]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)([CH3:41])[CH3:40])[CH:22]=2)=[CH:12][CH:11]=3)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 68509CumylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592338213-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-1H-indol-5-yl)benzoic acid

Product 1

HCID 592336602-(4-fluorophenyl)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)-1H-indole-3-carboxamideYield 70.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-1H-indol-5-yl)benzoic acid (12 mg, 0.031 mmol) and DIPEA (20 μL, 0.115 mmol) in 1,2-dichloroethane (0.5 mL)/DMF (0.1 mL) was added cumylamine (15 μL, 0.10 mmol) and HATU (15 mg, 0.039 mmol). The reaction was stirred at r.t. for 30 min, then the volatiles were evaporated and the residue was purified directly by prep HPLC. Concentration afforded the title compound as a white powder (11 mg, 68% yield). 1H NMR (500 MHz, MeOD) δ ppm 8.52 (s, 1H) 8.09 (d, J=7.93 Hz, 2H) 7.85 (d, J=7.63 Hz, 1H) 7.66-7.77 (m, 3H) 7.49-7.57 (m, 3H) 7.47 (d, J=8.24 Hz, 2H) 7.31 (t, J=7.78 Hz, 2H) 7.23 (t, J=8.85 Hz, 2H) 7.19 (t, J=7.32 Hz, 1H) 2.89 (s, 3H) 1.78 (s, 6H). LC/MS was performed on a Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=3 min, stop time=4 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.49 min, (ES+) m/z (MH+)=506. 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=15.29 min, purity=97%; column: Waters Xbridge Phenyl 3.5 μm 4.6×150 mm, Rt=11.59 min, purity=98%.

Workup

  1. customthe volatiles were evaporated
  2. customthe residue was purified directly by prep HPLC
  3. concentrationConcentration

Sources & evidence

ORD record
ord-abcf0a27c29e43dbbc894081cacecbc9
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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