Diisopropylethylamine → HCID 11626906, compound

HRID 1028510Notes

Reaction equation

HRID 1028510 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:31][CH3:32])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][NH:21][CH2:22][C@@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[NH2:24])[CH:9]=1)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl[C:43](Cl)([O:45]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:31][CH3:32])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:18])([F:19])[F:17])=[CH:12][C:11]=2[CH2:20][N:21]2[CH2:22][C@@H:23]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[NH:24][C:43]2=[O:45])[CH:9]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 68591310HCID 68591310, compound

Product 1

HCID 11626906HCID 11626906, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1R)—N2-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1-phenylethane-1,2-diamine (96.0 mg, 0.22 mmol) in CH2Cl2 (15 mL) was cooled to 0° C. and DIPEA (230 μL, 1.32 mmol) was added followed by triphosgene (32.6 mg, 0.11 mmol). After 45 minutes, the reaction was poured into saturated NaHCO3 (25 mL). The mixture was extracted with EtOAc (75 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 10 to 60% EtOAc/hexanes afforded (4R)-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-phenylimidazolidin-2-one. The minor enantiomer was removed by chiral HPLC using an AD chiral column and 15% IPA/heptanes to afford enantiomerically pure product. Rf=0.16 (40% EtOAc/hexanes). LCMS=469.3 (M+1)+. 1H NMR (CDCl3, 500 MHz) (atropisomers present in 1:1 ratio, doubling of some peaks observed) δ 7.65 (m, 1H), 7.54 (d, J=7.7 Hz, 1H), 7.21-7.36 (m, 71-1), 6.87-6.94 (m, 2H), 4.65-4.77 (m, 21-1), 4.10-4.49 (m, 2H), 3.71 & 3.72 (2 singlets, 3H), 3.49-3.53 (m, 1H), 2.94-2.97 (m, 1H), 2.87 (m, 1H), 1.19-1.24 (m, 6H).

Workup

  1. extractionThe mixture was extracted with EtOAc (75 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 10 to 60% EtOAc/hexanes

Sources & evidence

ORD record
ord-053843d8647a46b5800522ccae4f67f2
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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