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

HRID 492978Notes

Reaction equation

HRID 492978 reaction equation
[NH2:1][C:2]1[CH:28]=[CH:27][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][CH:19]([CH2:22][N:23]4[CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:29])[CH:3]=1.[C:30]1([CH2:36][C:37]([N:39]=[C:40]=[O:41])=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(OCC)C>CN(C)C=O.CCCCCC>[F:29][C:4]1[CH:3]=[C:2]([NH:1][C:40]([NH:39][C:37](=[O:38])[CH2:36][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:41])[CH:28]=[CH:27][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][N:23]3[CH2:24][CH2:25][CH2:26]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 12259960Phenylacetyl isocyanateHCID 866021764-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide

Product 1

HCID 576775254-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 4-(azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (30 mg) in N,N-dimethylformamide (1 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (0.901 ml) under a nitrogen atmosphere, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to give a residue, to which were added diethyl ether (1.5 ml) and hexane (3 ml) to suspend. The solid was filtered off and dried under aeration to provide the titled compound (14.0 mg) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (100 ml)
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a residue
  10. filtrationThe solid was filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-35345f7fd0ea43d0ada3d2c6cf6bbcd7
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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