(Diethylamino)sulfur trifluoride → HCID 86612968, compound

HRID 1993617Notes

Reaction equation

HRID 1993617 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([NH:33][C@H:34]2[CH2:38][CH2:37][CH2:36][C@H:35]2[OH:39])=O)([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.CCN(S(F)(F)F)CC>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]2[O:39][C@H:35]3[CH2:36][CH2:37][CH2:38][C@@H:34]3[N:33]=2)([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 86612969HCID 86612969, compound

Product 1

HCID 86612968HCID 86612968, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-((1S,2R)-2-hydroxycyclopentyl)urea (9 mg, 0.016 mmol) in CH2Cl2 (1 mL) was added DAST (3 mg, 0.02 mmol). The reaction mixture was stirred for 5 min and concentrated under vacuum. The residue was purified by preparative HPLC Shimadzu-Phenomenex Luna 5μ column, 21.2×100 mm eluting with 10-90% CH3CN (90% in H2O, 0.1% TFA) gradient over 15 min with flow rate 20 mL/min and UV detection at 220 nm to give (3aS,6aS)-N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]oxazol-2-amine as a white solid (8 mg, 91%). LCMS RT=3.27 min [M+H] 551.94 (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: 500 MHz 1H (CDCl3) 10.57 ppm, 1H, m; 8.54 ppm, 1H, m,; 7.67 ppm, 1H, m; 7.16 ppm, 5H, m; 7.05 ppm, 1H, m; 6.94 ppm, 1H, m; 6.67 ppm, 2H, m; 5.95 ppm, 1H, t; 5.19 ppm, 1H, t; 4.54 ppm, 1H, t; 3.87 ppm, 2H, m; 2.12 ppm, 1H, m; 1.91 ppm, 1H, m; 1.83 ppm, 1H, m; 1.68 ppm, 2H, m; 1.50 ppm, 1H, m.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe residue was purified by preparative HPLC Shimadzu-Phenomenex Luna 5μ column, 21.2×100 mm
  3. washeluting with 10-90% CH3CN (90% in H2O, 0.1% TFA) gradient over 15 min with flow rate 20 mL/min and UV detection at 220 nm

Sources & evidence

ORD record
ord-f0575bbee7c64e549e7d7472e3b654f6
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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