Diethyl Ether → 4-Methylpiperazine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

HRID 492809Notes

Reaction equation

HRID 492809 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:25])[CH:3]=1.[C:26]1([CH2:32][C:33]([N:35]=[C:36]=[O:37])=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(OCC)C>O1CCCC1.FC1C=C(NC(NC(=O)CC2C=CC=CC=2)=S)C=CC=1OC1N=CN=C(NC(N2CCCC2)=O)C=1>[F:25][C:4]1[CH:3]=[C:2]([NH:1][C:36]([NH:35][C:33](=[O:34])[CH2:32][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:37])[CH:24]=[CH:23][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)=[O:15])[CH:8]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 12259960Phenylacetyl isocyanateHCID 576775974-Methylpiperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide

Product 1

HCID 576774744-Methylpiperazine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amideYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 11248939Pyrrolidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amideSolvent

Procedure

To a solution of 4-methylpiperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (80 mg) in tetrahydrofuran (2.3 ml) was added a solution of phenylacetyl isocyanate in hexane (1.4 ml, Production Example 1), followed by stirring under a nitrogen atmosphere at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was dried over anhydrous sodium sulfate, and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:1, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to give a crude product, to which diethyl ether was then added to precipitate a solid. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (55.2 mg, 47%) as colorless powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (100 ml)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under a reduced pressure
  4. customThe residue was purified by silica gel column chromatography (FUJI Silysia NH, eluent
  5. additionFractions containing the target compound
  6. concentrationwere concentrated
  7. customto give a crude product
  8. customto precipitate a solid
  9. filtrationThe solid was filtered off
  10. washwashed with diethyl ether
  11. customdried under aeration

Sources & evidence

ORD record
ord-b5c7a8ff224d4d98808bbb1601d4e1e4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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