Diisopropylethylamine → Ly-3031207

HRID 889545Notes

Reaction equation

HRID 889545 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:7][C:3]=1[C:4]([OH:6])=O.S(O)(O)(=O)=O.[NH2:24][C:25]1[NH:26][CH:27]=[CH:28][N:29]=1.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>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:7][C:3]=1[C:4]([NH:24][C:25]1[NH:26][CH:27]=[CH:28][N:29]=1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584832082-Chloro-5-[(2,2-dimethylpropanamido)methyl]benzoic acid

Product 1

HCID 57382526Ly-3031207Yield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a thermally controlled reaction vessel, add 2-chloro-5-[(2,2-dimethylpropanoylamino)methyl]benzoic acid (420 g, 1.56 mol, 1.0 equiv), 2-aminoimidazole monosulfate (349 g, 1.87 mol, 1.2 equiv), N,N-dimethylformamide (2.94 L), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (722 g, 2.18 mol, 1.4 equiv), and N,N-diisopropylethylamine (869 mL, 4.98 mol, 3.2 equiv). Heat the resulting suspension to an internal temperature of 80° C. for 18 hours. Cool the reaction mixture to 10° C., pour the mixture into ice water (14 L), and stir for 90 min. Collect the solids by filtration, dry the material in air for 24 h, and in a vacuum oven at 50° C. for 24 h. Slurry the solid material in isopropanol (7 L), heat to an internal temperature of 73° C. for 3 h, and cool to 10° C. Filter the suspension to isolate the solid material. Dry the material in air for 24 h and in a vacuum oven at 55° C. for 48 h to give the title compound as an off-white solid (435 g, 83.4%). 1H NMR (DMSO-d6, 400 MHz): δ 11.84 (s, 2H), 8.13 (t, 1H, J=6.0 Hz), 7.47 (d, 1H, J=8.3 Hz), 7.40 (d, 1H, J=1.7 Hz), 7.31 (dd, 1H, J=8.3, 2.0 Hz), 6.73 (s, 2H), 4.27 (d, 2H, J=5.9 Hz), 1.12 (s, 9H). MS (m/z) (35Cl/37Cl) 335/337 (M+1).

Workup

  1. customTo a thermally controlled reaction vessel
  2. temperatureCool the reaction mixture to 10° C.
  3. customCollect the solids
  4. filtrationby filtration
  5. customdry the material in air for 24 h
  6. waitin a vacuum oven at 50° C. for 24 h
  7. temperatureheat to an internal temperature of 73° C. for 3 h
  8. temperaturecool to 10° C
  9. filtrationFilter the suspension
  10. customto isolate the solid material
  11. customDry the material in air for 24 h

Sources & evidence

ORD record
ord-c7d254031a65442b84cc9b96b1e5f555
Source dataset
uspto-grants-2012_08
Patent number
US08252831B2

Reaction notes

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