Tris(hydroxymethyl)aminomethane → HCID 16049867, compound

HRID 2059811Notes

Reaction equation

HRID 2059811 reaction equation
[NH2:1][CH2:2][CH:3]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:4]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[C:5]([N:7]([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])=[O:6].[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][N:34]=[C:35]=[O:36].CCN(C(C)C)C(C)C.C(O)C(N)(CO)CO>C(Cl)Cl>[CH:11]([N:7]([CH:8]([CH3:9])[CH3:10])[C:5]([CH:4]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[CH:3]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:2][NH:1][C:35]([NH:34][CH2:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[F:26])=[O:36])=[O:6])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 81531DiisopropylethylamineHCID 6434981-Fluoro-2-(isocyanatomethyl)benzeneHCID 57429230HCID 57429230, compound

Product 1

HCID 16049867HCID 16049867, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-amino-N,N-diisopropyl-3-phenyl-2-(pyridin-3-yl)butanamide (0.030 g, 0.09 mmol) in dry DCM (2 mL) was added 1-fluoro-2-(isocyanatomethyl)benzene (0.028 g, 0.18 mmol), and DIPEA (0.023 mL, 0.135 mmol). The reaction mixture was agitated for 15 h at room temperature before adding PS-trisamine (0.022 g, 0.09 mmol) and agitating for 1 h at room temperature. The crude product was then filtered to remove the solid phase and concentrated. Purification of enantiomers by ChiralPak AD (n-hexanes/EtOH, 85:15) yielded (−)-1-(3-(diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea as a foamy, off-white solid. Analytical LCMS: single peak (214 nm), 2.523 min. 1H NMR (CDCl3, 300 MHz) δ 8.26 (d, J=4.5 Hz, 1H), 8.03 (s, 1H), 7.38-7.42 (m, 2H), 7.19-7.25 (m, 1H), 6.99-7.13 (m, 6H), 6.91-6.93 (m, 2H), 4.54-4.59 (m, 1.37 (d, J=6.9 Hz, 3H), 1.26 (d, J=6.9 Hz, 3H), 1.19 (d, J=6.9 Hz, 3H), 0.60 (d, J=6.3 Hz, 3H); HRMS m/z 491.2841 (C29H35FN4O2+H requires 491.2817).

Workup

  1. stirringagitating for 1 h at room temperature
  2. filtrationThe crude product was then filtered
  3. customto remove the solid phase
  4. concentrationconcentrated
  5. customPurification of enantiomers by ChiralPak AD (n-hexanes/EtOH, 85:15)

Sources & evidence

ORD record
ord-6a93bf64ce1c4f56b601e04fd71e77e4
Source dataset
uspto-grants-2012_10
Patent number
US08278317B2

Reaction notes

Loading…