Chloride → HCID 58920315, compound

HRID 1365528Notes

Reaction equation

HRID 1365528 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:41])[NH:32][CH:33]([C:37]([F:40])([F:39])[F:38])[C:34]([NH2:36])=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.CS(C)=O.[Cl-].CCN(CC)CC>C(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([NH:32][CH:33]([C:34]#[N:36])[C:37]([F:39])([F:38])[F:40])=[O:41])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:25])[F:26])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 312ChlorideHCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 58920187HCID 58920187, compound

Product 1

HCID 58920315HCID 58920315, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)-3,3,3-trifluoropropanamide (15 mg, 0.024 mmol) in DCM (0.5 mL) was added DMSO (3.74 mg, 0.048 mmol). The reaction mixture was cooled to −78° C. and oxaly chloride (18.4 μL, 2M in DCM, 0.04 mmol) was added. After 15 min at −78° C., NEt3 (10 μL, 0.072 mmol) was added. The reaction mixture was stirred for 1 h and H2O was added to quench the reaction. The reaction mixture was concentrated and the crude mixture was purified by preparative HPLC Shimadzu-Phenomenex C18 column, 20×100 mm eluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 20 mL/min and UV detection at 220 nm. 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(1-cyano-2,2,2-trifluoroethyl)urea was isolated as a pale yellow solid (7 mg, 50% yield). LCMS: RT=3.96 min [M+H] 593.11 (LCMS Method 1); NMR: 400 MHz 1H (CDCl3) 8.27 ppm, 1H, m; 7.72 ppm, 1H, m; 7.63 ppm, 1H, d, J=12.6 Hz; 7.12 ppm, 6H, m; 6.91 ppm, 1H, m; 6.52 ppm, 2H, dd, J=20.2, 6.8 Hz; 5.81 ppm, 2H, m; 5.23 ppm, 1H, dd, J=27.3, 10.1 Hz; 4.33 ppm, 1H, dd, J=12.9, 3.3 Hz; 3.52 ppm, 1H, m.

Workup

  1. customto quench
  2. customthe reaction
  3. concentrationThe reaction mixture was concentrated
  4. customthe crude mixture was purified by preparative HPLC Shimadzu-Phenomenex C18 column, 20×100 mm
  5. washeluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 20 mL/min and UV detection at 220 nm

Sources & evidence

ORD record
ord-6781dff97801451083407365cef65c24
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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