HCID 178465306, compound → HCID 178465307, compound

HRID 576908Notes

Reaction equation

HRID 576908 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[NH:11][C:10]2[C:12]([CH:27]3[CH2:31][CH2:30][CH2:29][O:28]3)=[C:13]([F:26])[C:14]([C:16]3[CH:17]=[N:18][C:19]([C:22]([OH:25])([CH3:24])[CH3:23])=[N:20][CH:21]=3)=[CH:15][C:9]=2[N:8]=1)=[O:5])[CH3:2]>CCO.CCOCC>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[NH:11][C:10]2[C:12]([C@H:27]3[CH2:31][CH2:30][CH2:29][O:28]3)=[C:13]([F:26])[C:14]([C:16]3[CH:17]=[N:18][C:19]([C:22]([OH:25])([CH3:24])[CH3:23])=[N:20][CH:21]=3)=[CH:15][C:9]=2[N:8]=1)=[O:5])[CH3:2]

Participants

3

Reactant 1

HCID 178465306HCID 178465306, compound

Product 1

HCID 178465307HCID 178465307, compoundYield 45.4%

Reagents, catalysts & solvents 1

HCID 21585056Diethyl ether ethanolSolvent

Procedure

A racemic sample of 1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-tetrahydrofuran-2-yl-1H-benzimidazol-2-yl]urea (133.60 g) was resolved on a CHIRALPAK® IC® column (by Chiral Technologies) eluting with DCM/MeOH/TEA (60/40/0.1) at 25° C. giving the desired enantiomer as an off-white solid (66.8 g, 99.8% HPLC purity, 99+% ee). Analytical chiral HPLC retention time was 7.7 min (CHIRALPAK® IC® 4.6×250 mm column, 1 mL/min flow rate, 30° C.). The solid was suspended in 2:1 EtOH/Et2O (5 volumes), stirred for 10 minutes, collected by filtration, washed with 2:1 EtOH/Et2O, and dried under reduced pressure giving a white solid (60.6 g). 1H NMR (300 MHz, MeOD) δ 8.95 (d, J=1.6 Hz, 2H), 7.45 (d, J=6.5 Hz, 1H), 5.38 (br.s, 1H), 4.27 (dd, J=14.9, 7.1 Hz, 1H), 4.01 (dd, J=15.1, 7.0 Hz, 1H), 3.37-3.29 (m, 2H), 2.55 (br.s, 1H), 2.19-2.07 (m, 2H), 2.02-1.82 (br.s, 1H), 1.63 (s, 6H), 1.21 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. washeluting with DCM/MeOH/TEA (60/40/0.1) at 25° C.
  2. customgiving the desired enantiomer as an off-white solid (66.8 g, 99.8% HPLC purity, 99+% ee)
  3. customAnalytical chiral HPLC retention time was 7.7 min (CHIRALPAK® IC® 4.6×250 mm column, 1 mL/min flow rate, 30° C.)
  4. filtrationcollected by filtration
  5. washwashed with 2:1 EtOH/Et2O
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-5f1107f56140409087647475bd8ed172
Source dataset
uspto-grants-2015_05
Patent number
US09040542B2

Reaction notes

Loading…