Diisopropylethylamine → HCID 70913255, compound

HRID 2208848Notes

Reaction equation

HRID 2208848 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:26][CH3:27])[C:15]2[C:16]([CH3:25])=[C:17]([CH:21]=[C:22]([Cl:24])[CH:23]=2)[C:18](O)=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[NH2:70][CH2:71][C:72]1[C:73](=[O:80])[NH:74][C:75]([CH3:79])=[CH:76][C:77]=1[CH3:78]>CN(C=O)C.CCOC(C)=O>[Cl:24][C:22]1[CH:21]=[C:17]([C:18](=[O:19])[NH:70][CH2:71][C:72]2[C:73](=[O:80])[NH:74][C:75]([CH3:79])=[CH:76][C:77]=2[CH3:78])[C:16]([CH3:25])=[C:15]([N:14]([CH2:26][CH3:27])[CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:13][CH2:12]2)[CH:23]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 70874117HCID 70874117, compound

Product 1

HCID 70913255HCID 70913255, compoundYield 89.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-({1-[(tert-butoxy)carbonyl]piperidin-4-yl}(ethyl)amino)-5-chloro-2-methylbenzoic acid (60 mg, 0.15 mmol) in DMF (2 ml) at room temperature under nitrogen was added PyBOP (94 mg, 0.18 mmol) followed by N-ethyl-N-(propan-2-yl)propan-2-amine (40 μl, 0.23 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 28 mg, 0.17 mmol). After stirring for 1 hour at room temperature EtOAc (30 ml) was added to the reaction mixture and this was then washed with deionized water (5 ml) followed by saturated NaHCO3(aq) (3×5 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (2 g silica, Isolute cartridge, gradient of eluents; 100% EtOAc to 96:4 EtOAc:MeOH) to give 71 mg (88%) of the title compound as a pale yellow solid. LC-MS 97%, m/z=531.1/533.1, 1H NMR (250 MHz, Chloroform-d) δ ppm 11.17 (1H, br. s.), 7.11-7.18 (1H, m), 7.06 (2H, dd, J=7.46, 2.28 Hz), 5.96 (1H, s), 4.53 (2H, d, J=5.94 Hz), 3.93-4.14 (2H, m), 2.97-3.08 (2H, m), 2.78-2.88 (1H, m), 2.68 (2H, t, J=11.57 Hz), 2.39 (3H, s), 2.26 (3H, s), 2.24 (3H, s), 1.71 (2H, d, J=11.27 Hz), 1.52 (2H, br. s.), 1.45 (9H, s), 0.86 (3H, t, J=6.93 Hz).

Workup

  1. additionwas added to the reaction mixture
  2. washthis was then washed with deionized water (5 ml)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by FCC (2 g silica, Isolute cartridge, gradient of eluents; 100% EtOAc to 96:4 EtOAc:MeOH)

Sources & evidence

ORD record
ord-cdaaac8b17ae4b139b756ce241ebf226
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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