Water → HCID 25195956, compound

HRID 1670297Notes

Reaction equation

HRID 1670297 reaction equation
C([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21](=[O:30])[CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:19])=[CH:13][C:12]=2[Cl:31])[CH:7]=[CH:6][N:5]=1)(=O)N.O.[N:33]1C=CC=CC=1.FC(F)(F)C(OC1C(OC(=O)C(F)(F)F)=C(I)C=CC=1)=O>CN(C=O)C>[ClH:31].[NH2:33][C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21](=[O:30])[CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:19])=[CH:13][C:12]=2[Cl:31])[CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 11711920HCID 11711920, compoundHCID 12041285Bistrifluoroacetoxyiodobenzene

Product 1

HCID 25195956HCID 25195956, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-(2-carbamoylpyridin-4-yloxy)-3-chlorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea (Example 90, 27 mg, 0.06 mmol) in DMF (1.0 mL) were added H2O (2.2 mg, 0.12 mmol), pyridine (0.04 mL) and bis(trifluoroacetoxy)iodobenzene (Aldrich, 39 mg, 0.09 mmol) at room temperature. The solution was allowed to stir overnight and then it was purified on prep HPLC to give the desired product, which was further converted to 1-(4-(2-aminopyridin-4-yloxy)-3-chlorophenyl)-3-(2-(4-fluorophenyl)acetyl)urea hydrochloride (19 mg, 70% yield) by the addition of 1N HCl solution (0.5 mL). 1H NMR (DMSO-d6) δ 13.50 (s, 1H), 11.02 (s, 1H), 10.57 (s, 1H), 7.80-7.95 (m, 4H), 7.55 (m, 1H), 7.37 (m, 1H), 7.30 (m, 2H), 7.11 (m, 2H), 6.60 (m, 1H), 6.00 (s, 1H), 3.70 (s, 2H); MS (ESI+): m/z 415.16 (M+H)+.

Workup

  1. customit was purified on prep HPLC

Sources & evidence

ORD record
ord-32ff84408d204fb7a5b9721ebc932311
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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