Ammonium Hydroxide → HCID 72463202, compound

HRID 1365530Notes

Reaction equation

HRID 1365530 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:30][C:31](=[O:40])[NH:32][C:33]([CH3:39])([CH3:38])[CH2:34][C:35]([OH:37])=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.C1C=CC2N(O)N=[N:47]C=2C=1.CCN=C=NCCCN(C)C.[NH4+].[OH-]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:30][C:31](=[O:40])[NH:32][C:33]([CH3:38])([CH3:39])[CH2:34][C:35]([NH2:47])=[O:37])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[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

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 72463369HCID 72463369, compound

Product 1

HCID 72463202HCID 72463202, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(3-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)-3-methylbutanoic acid (17.4 mg, 0.03 mmol) in DMF (1 mL) was added HOBt (20 mg, 0.148 mmol) and EDCI (29 mg, 0.151 mmol). The resulting mixture was stirred at room temperature over night, followed by addition of NH4OH (1 mL). After 5 min, the reaction mixture was concentrated and the residue was purified by preparative HPLC Shimadzu-AXIA column, 30×100 mm eluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm to give 3-(3-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)-3-methylbutanamide as a white foam (15.5 mg, 88% yield). LCMS: RT=1.99 min [M+H] 585.3 (LCMS Method 2); NMR: 400 MHz 1H (CDCl3) 8.30 ppm, 1H, d, J=2.0 Hz; 7.75 ppm, 1H, dd, J=8.7, 2.4 Hz; 7.44 ppm, 1H, br. s; 7.16 ppm, 5H, m; 6.99 ppm, 1H, s; 6.92 ppm, 1H, d, J=8.8 Hz; 6.67 ppm, 1H, br. s; 6.57 ppm, 2H, d, J=7.1 Hz; 5.97 ppm, 1H, t, J=53 Hz; 4.10 ppm, 1H, d, J=12.9 Hz; 3.63 ppm, 1H, d, J=13.1 Hz; 2.97 ppm, 1H, d, d=13.1 Hz; 2.44 ppm, 1H, d, J=13.1 Hz; 1.47 ppm, 3H, s; 1.36 ppm, 3H, s.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe residue was purified by preparative HPLC Shimadzu-AXIA column, 30×100 mm
  3. washeluting with 30-100% MeOH (90% in H2O, 0.1% TFA) gradient over 12 min with flow rate 40 mL/min and UV detection at 220 nm

Sources & evidence

ORD record
ord-46836244c056445c8b8b8a2e65827ca1
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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