(S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamate → 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-((1R,2R)-2-hydroxycyclopentyl)urea

HRID 1993616Notes

Reaction equation

HRID 1993616 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[OH:14].[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C@@:22]([NH:44][C:45](=O)[O:46]C2C=CC([N+]([O-])=O)=CC=2)([C:30]2[CH:35]=[C:34]([O:36][C:37]([F:42])([F:41])[CH:38]([F:40])[F:39])[CH:33]=[C:32]([F:43])[CH:31]=2)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:20][CH:21]=1>C(Cl)Cl>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C@@:22]([NH:44][C:45]([NH:8][C@@H:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[OH:14])=[O:46])([C:30]2[CH:35]=[C:34]([O:36][C:37]([F:42])([F:41])[CH:38]([F:40])[F:39])[CH:33]=[C:32]([F:43])[CH:31]=2)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:20][CH:21]=1

Participants

4

Reactant 2

HCID 59134633(S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamateHCID 86612967(1R,2R)-2-Amino-cyclopentanol Trifluoroacetic Acid Salt

Product 1

HCID 591347221-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-((1R,2R)-2-hydroxycyclopentyl)ureaYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(1R,2R)-2-aminocyclopentanol TFA salt (107 mg, 0.50 mmol) in DCM (2 mL) was added TEA (140 μL, 1.0 mmol), followed by the addition of crude (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamate (162 mg, 0.27 mmol). The reaction mixture was stirred at room temperature for 18 h, concentrated and purified by ISCO chromatography (12 g column) using hexanes/EtOAc (0-60%) over 30 min to give 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-((1R,2R)-2-hydroxycyclopentyl)urea as a pale yellow solid (110 mg, 73% yield). LCMS RT=3.90 min [M+H] 570.24 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 8.24 ppm, 1H, d, J=2.27 Hz; 7.64 ppm, 1H, dd, J=8.59, 2.27 Hz; 7.20 ppm, 1H, m; 7.12 ppm, 6H, m; 6.87 ppm, 1H, d, J=8.59 Hz; 6.62 ppm, 2H, d, J=7.07 Hz; 5.87 ppm, 1H, tt, J=53.02, 2.56 Hz; 4.91 ppm, 1H, d, J=4.04 Hz; 4.40 ppm, 1H, d, J=12.88 Hz; 3.97 ppm, 1H, q, J=6.57 Hz; 3.66 ppm, 1H, m; 3.55 ppm, 1H, d, J=12.63 Hz; 1.99 ppm, 1H, m; 1.66 ppm, 3H, m; 1.30 ppm, 2H, m.

Workup

  1. concentrationconcentrated
  2. custompurified by ISCO chromatography (12 g column)
  3. customover 30 min

Sources & evidence

ORD record
ord-26fd7fc8d3e94cf680a114e3550ee3c3
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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