Dimethylformamide → HCID 57677318, compound

HRID 492827Notes

Reaction equation

HRID 492827 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:28])[CH2:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[O:19])=[C:11]([CH3:29])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:30][N:31]([CH3:34])[CH:32]=[O:33].[CH2:35]([N:37]([CH2:40][CH3:41])[CH2:38][CH3:39])[CH3:36].Cl[C:43](OC1C=CC=CC=1)=O>O1CCCC1.C(O)C.C(OCC)C.C(OCC)(=O)C>[F:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:18](=[O:19])[CH2:17][C:16]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:32]([N:31]4[CH2:34][CH2:43][CH:35]([N:37]5[CH2:40][CH2:41][CH2:39][CH2:38]5)[CH2:36][CH2:30]4)=[O:33])[CH:7]=3)=[CH:10][C:11]=2[CH3:29])=[O:28])=[CH:22][CH:23]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 23153052HCID 23153052, compound

Product 1

HCID 57677318HCID 57677318, compoundYield 71.4%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[4-(2-aminopyridin-4-yloxy)-2-methylphenyl]-N′-(4-fluorophenyl)malonamide (60 mg) in tetrahydrofuran (6 ml)-N,N-dimethylformamide (0.090 ml) was added triethylamine (0.042 ml), and then phenyl chloroformate (0.0378 ml) was added thereto while cooling in an ice water bath, followed by stirring for 20 min. The reaction mixture was concentrated under a reduced pressure. To a suspension of the residue in N,N-dimethylformamide (2.4 ml) was added 4-(1-pyrrolidinyl)piperidine (93 mg), followed by stirring at room temperature for 5 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a 1 N aqueous solution of sodium hydroxide (30 ml). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and subjected to silica gel filtration (FUJI Silysia NH). The filtrate was concentrated under a reduced pressure to give a residue, which was then suspended in ethanol (0.5 ml) and ethyl acetate (1 ml)-diethyl ether (5 ml). The solid was filtered off, washed with diethyl ether and dried under aeration to provide the titled compound (62.4 mg, 71.4%) as colorless powder.

Workup

  1. temperaturewhile cooling in an ice water bath
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. additionTo a suspension of the residue in N,N-dimethylformamide (2.4 ml)
  4. additionwas added 4-(1-pyrrolidinyl)piperidine (93 mg)
  5. stirringby stirring at room temperature for 5 hrs
  6. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationsubjected to silica gel filtration (FUJI Silysia NH)
  10. concentrationThe filtrate was concentrated under a reduced pressure
  11. customto give a residue, which
  12. filtrationThe solid was filtered off
  13. washwashed with diethyl ether
  14. customdried under aeration

Sources & evidence

ORD record
ord-ea9c04fabb264e549937fb336558d046
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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