3-Pyridinemethanamine → (s)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-n-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 1882422Notes

Reaction equation

HRID 1882422 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]3[S:14][C:15]([C:19](O)=[O:20])=[C:16]([CH3:18])[N:17]=3)[C:8]2=[O:22])=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[N:66]1[CH:71]=[CH:70][CH:69]=[C:68]([CH2:72][NH2:73])[CH:67]=1>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C@@H:11]([CH3:12])[CH2:10][N:9]([C:13]3[S:14][C:15]([C:19]([NH:73][CH2:72][C:68]4[CH:67]=[N:66][CH:71]=[CH:70][CH:69]=4)=[O:20])=[C:16]([CH3:18])[N:17]=3)[C:8]2=[O:22])=[CH:23][CH:24]=1

Participants

7

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57919976(S)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 44193690(s)-2-(3-(4-Fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methyl-n-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-(3-(4-fluorobenzyl)-4-methyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (0.11 g, 0.30 mmol) in anhydrous tetrahydrofuran (3.0 mL) was added 1-hydroxybenzotriazole (HOBt) (0.08 g, 0.60 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (0.19 g, 0.60 mmol), N,N-diisopropylethylamine (0.23 g, 1.80 mmol) and pyridin-3-ylmethanamine (0.05 g, 0.45 mmol). The resulting mixture was stirred at ambient temperature for 16 h and concentrated in vacuo. The residue was diluted in ethyl acetate (100 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL), dried over anhydrous sodium sulphate and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluted with 2-8% methanol in dichloromethane to afford the title compound as a colorless solid (0.09 g, 70%): mp 67-70° C. (hexanes/diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.57 (t, J=5.9 Hz, 1H), 8.53 (d, J=1.9 Hz, 1H), 8.45 (dd, J=4.8, 1.5 Hz, 1H), 7.72-7.69 (m, 1H), 7.40-7.34 (m, 3H), 7.18 (dd, J=8.8, 8.8 Hz, 2H), 4.59 (d, J=15.6 Hz, 1H), 4.40 (d, J=5.9 Hz, 2H), 4.30 (d, J=15.6 Hz, 1H), 4.19 (dd, J=10.1, 9.1 Hz, 1H), 3.80-3.69 (m, 1H), 3.55 (dd, J=10.1, 6.2 Hz, 1H), 2.47 (s, 3H), 1.22 (d, J=6.2 Hz, 3H); 13C NMR (75 MHz, DMSO-d6) δ 161.5 (d, 1JC-F=244 Hz), 161.8, 157.2, 154.9, 151.2, 148.8, 148.0, 135.1, 135.1, 133.1 (d, 4JC-F=3 Hz), 130.0 (d, 3JC-F=8 Hz), 123.5, 117.6, 115.4 (d, 2JC-F=21 Hz), 49.4, 48.6, 43.7, 40.4, 18.4, 17.1; MS (ES+) m/z 439.9 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted in ethyl acetate (100 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (20 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by column chromatography
  8. washeluted with 2-8% methanol in dichloromethane

Sources & evidence

ORD record
ord-051b4ee892044034b2db2794d29a1c2f
Source dataset
uspto-grants-2012_11
Patent number
US08318949B2

Reaction notes

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