Diisopropylethylamine → HCID 70873846, compound

HRID 2208841Notes

Reaction equation

HRID 2208841 reaction equation
[Br:1][C:2]1[C:10]([N:11]([CH2:18][CH3:19])[CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:9][C:8]([Cl:20])=[CH:7][C:3]=1[C:4]([OH:6])=O.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.[NH2:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[C:10]([N:11]([CH2:18][CH3:19])[CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:9][C:8]([Cl:20])=[CH:7][C:3]=1[C:4]([NH:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71])=[O:6]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 70874054HCID 70874054, compound

Product 1

HCID 70873846HCID 70873846, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-bromo-5-chloro-3-[ethyl(oxan-4-yl)amino]benzoic acid (109 mg, 0.3 mmol) in DMF (3 ml) at room temperature under nitrogen was added PyBOP (187 mg, 0.36 mmol) followed by N-ethyl-N-(propan-2-yl)propan-2-amine (78 μl, 0.45 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 56 mg, 0.33 mmol). After stirring for 1 hour at room EtOAc (30 ml) was added to the reaction mixture and this was then washed with deionized water (2×10 ml) followed by saturated NaHCO3(aq) (2×10 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified twice by FCC (5 g silica, Isolute cartridge, gradient of eluents; 100% DCM to 98:2 DCM:MeOH). The sample was dried in a vacuum oven for 18 hours to give 103 mg (65%) of the title compound as a pale yellow solid. LC-MS 94%, m/z=496.0/498.0/500.0, 1H NMR (500 MHz, Chloroform-d) δ 11.00 (s, 1H), 7.20-7.10 (m, 1H), 7.10-7.05 (m, 2H), 5.94 (s, 1H), 4.54 (d, J=5.9 Hz, 2H), 3.96 (d, J=11.4 Hz, 2H), 3.42-3.26 (m, 2H), 3.28-3.12 (m, 1H), 3.09 (q, J=7.0 Hz, 2H), 2.39 (s, 3H), 2.23 (s, 3H), 1.72 (td, J=8.5, 3.8 Hz, 4H), 0.90 (t, J=7.0 Hz, 3H).

Workup

  1. additionwas added to the reaction mixture
  2. washthis was then washed with deionized water (2×10 ml)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified twice by FCC (5 g silica, Isolute cartridge, gradient of eluents; 100% DCM to 98:2 DCM:MeOH)
  7. customThe sample was dried in a vacuum oven for 18 hours

Sources & evidence

ORD record
ord-9c6781829df342d9998df3b3f69d23b3
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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