2-Propenoic acid, 3-phenyl- → (E)-5-((1-cinnamoylazetidin-3-yl)amino)-2'-(methylamino)-[3,4'-bipyridin]-6(1H)-one

HRID 2283470Notes

Reaction equation

HRID 2283470 reaction equation
Br.Br.[NH:3]1[CH2:6][CH:5]([NH:7][C:8]2[C:13](=[O:14])[NH:12][CH:11]=[C:10]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH3:22])[CH:16]=3)[CH:9]=2)[CH2:4]1.[C:23](O)(=[O:32])[CH:24]=[CH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.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>CN(C=O)C>[C:23]([N:3]1[CH2:6][CH:5]([NH:7][C:8]2[C:13](=[O:14])[NH:12][CH:11]=[C:10]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH3:22])[CH:16]=3)[CH:9]=2)[CH2:4]1)(=[O:32])/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 87842-Propenoic acid, 3-phenyl-HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1182509885-(azetidin-3-ylamino)-2'-(methylamino)-[3,4'-bipyridin]-6(1H)-one di-hydrobromide

Product 1

HCID 118250957(E)-5-((1-cinnamoylazetidin-3-yl)amino)-2'-(methylamino)-[3,4'-bipyridin]-6(1H)-oneYield 55.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(azetidin-3-ylamino)-2′-(methylamino)-[3,4′-bipyridin]-6(1H)-one di-hydrobromide (80.0 mg, 0.185 mmol) in DMF (1 mL) was added cinnamic acid (60 mg, 0.41 mmol), HATU (105 mg, 0.277 mmol), and DIPEA (120 mg, 0.924 mmol). The reaction mixture was stirred at RT under nitrogen for 16 h. The residue was purified by Prep HPLC (ethyl acetate/hexane) to afford (E)-5-((1-cinnamoylazetidin-3-yl)amino)-2′-(methylamino)-[3,4′-bipyridin]-6(1H)-one (41 mg, 55%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 11.25 (s, 1H), 8.11 (d, J=5.4 Hz, 1H), 7.69 (d, J=15.6 Hz, 1H), 7.52 (dd, J=6.7, 3.0 Hz, 2H), 7.37 (dd, J=5.0, 2.0 Hz, 3H), 7.09 (d, J=2.2 Hz, 1H), 6.63 (dd, J=5.4, 1.6 Hz, 1H), 6.48 (d, J=15.6 Hz, 1H), 6.38 (d, J=1.9 Hz, 2H), 5.48 (d, J=6.6 Hz, 1H), 4.80-4.65 (m, 2H), 4.63-4.50 (m, 1H), 4.46-4.32 (m, 1H), 4.26-4.05 (m, 2H), 2.98 (d, J=4.8 Hz, 3H); MS (ES) m/z 402 (M+H).

Workup

  1. customThe residue was purified by Prep HPLC (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-10138713448a4085879bcf43135177ac
Source dataset
uspto-grants-2015_09
Patent number
US09145393B2

Reaction notes

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