Triethylamine → HCID 57677406, compound

HRID 492729Notes

Reaction equation

HRID 492729 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[N:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:27](OC1C=CC=CC=1)=[O:28].[N:36]1([CH:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:40][CH2:39][CH2:38][CH2:37]1>O1CCCC1.CN(C)C=O>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:1][C:27]([N:44]2[CH2:45][CH2:46][CH:41]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:42][CH2:43]2)=[O:28])[CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

Product 1

HCID 57677406HCID 57677406, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine (50 mg) was dissolved in tetrahydrofuran (3 ml) under a nitrogen atmosphere, and then triethylamine (0.056 ml) and phenyl chloroformate (0.050 ml) were added dropwise thereto, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (3 ml). 4-(Pyrrolidin-1-yl)piperidine (123 mg) was added thereto, followed by stirring at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:5). The solvent was evaporated under a reduced pressure, and dried in vacuum to provide a crude product of 4-(pyrrolidin-1-yl)piperidine-1-carboxylic acid [6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl]amide. The crude product (86 mg) was dissolved in tetrahydrofuran (2 ml)-methanol (2 ml), and then 10% palladium carbon (43 mg) was added thereto under a nitrogen atmosphere, followed by replacing with hydrogen inside the system and stirring overnight. After replacing with nitrogen inside the system, the reaction mixture was filtered to remove the catalyst, which was washed with methanol. The filtrate was concentrated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:5, then ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to provide the titled compound (53.5 mg, 66.8%).

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue, which
  3. stirringby stirring at room temperature for 2 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate
  5. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under a reduced pressure
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:5)
  10. customThe solvent was evaporated under a reduced pressure
  11. customdried in vacuum

Sources & evidence

ORD record
ord-03c98e54aa1d4081bed56443335cf9ca
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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