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

HRID 492793
Notes
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Reaction equation

HRID 492793 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]([N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][C:3]=1[F:29].[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[C:45]1([CH2:51][C:52]([N:54]=[C:55]=[S:56])=[O:53])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.CCCCCC>[F:29][C:3]1[CH:4]=[C:5]([CH:27]=[CH:28][C:2]=1[NH:1][C:55]([NH:54][C:52](=[O:53])[CH2:51][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[S:56])[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]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 12454157Phenylacetyl isothiocyanateHCID 576775624-(Pyrrolidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide

Product 1

HCID 576773594-(Pyrrolidin-1-yl)piperidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide
Yield 18%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8058HexaneSolvent

Procedure

4-(Pyrrolidin-1-yl)piperidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide was dissolved in ethanol (3.0 ml), and then (S)-(+)-10-camphorsulfonic acid (75.5 mg) was added thereto, followed by stirring at room temperature for 15 min. A solution of phenylacetyl isothiocyanate (45.5 mg) in toluene (3.0 ml) was added thereto, followed by stirring at room temperature for 2.5 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with brine (30 ml×3), 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; heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate). Fractions containing the target compound were concentrated to give a solid, to which diethyl ether (3 ml) and hexane (3 ml) in this order were then added to suspend. The solid was filtered off, washed with diethyl ether (1 ml), and dried under aeration to provide the titled compound (17.8 mg, 18%) as colorless powder.

Workup

  1. stirringby stirring at room temperature for 2.5 hrs
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  3. washThe organic layer was washed with brine (30 ml×3)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  8. additionFractions containing the target compound
  9. concentrationwere concentrated
  10. customto give a solid
  11. filtrationThe solid was filtered off
  12. washwashed with diethyl ether (1 ml)
  13. customdried under aeration

Sources & evidence

ORD record
ord-df71f61b6a3a4969a545c8dcb414d5f3
Source dataset
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07531532B2

Reaction notes

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