Triethylamine → HCID 21110114, compound

HRID 1766370Notes

Reaction equation

HRID 1766370 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][C:13](=[O:15])[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)[C:11]([CH3:26])=[C:10]2[C:27]([OH:29])=[O:28])=[CH:5][CH:4]=1)#[N:2].C1N=CN(C(N2C=NC=C2)=O)C=1.O[CH2:43][CH2:44][N:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1.C(N(CC)CC)C>CN(C)C=O.O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH2:14][C:13](=[O:15])[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:24])([F:25])[F:23])[CH:17]=3)[C:11]([CH3:26])=[C:10]2[C:27]([O:29][CH2:43][CH2:44][N:45]2[CH2:49][CH2:48][CH2:47][CH2:46]2)=[O:28])=[CH:7][CH:8]=1)#[N:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 762881-PyrrolidineethanolHCID 21110134HCID 21110134, compound

Product 1

HCID 21110114HCID 21110114, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 40 mg (0.1 mmol) of the compound of Example 47 in 0.3 ml dry dimethylformamide are added 48.6 mg (0.3 mmol) N,N-carbonyldiimidazole. After allowing the reaction mixture to stand for one hour, the reaction mixture is diluted with water and extracted with ethyl acetate. After drying with magnesium sulfate, the solvent is evaporated off in vacuo. To the residue are added 0.5 ml (492 mg, 4.28 mmol) 1-(2-hydroxyethyl)pyrrolidin and 10 μl (0.07 mmol) triethylamine. The reaction mixture is stirred at 100° C. for one hour. Then the reaction mixture is filtered and purified by preparative HPLC (column: Nucleosil 100-5 C 18 Nautilus 20 mm×50 mm, 5 μm; solvent A: acetonitrile, solvent B: water+0.1% formic acid; gradient: 0 min 10% A, 2 min 10% A, 6 min 90% A, 7 min 90% A, 7.1 min 10% A, 8 min 10% A; wavelength: 220 nm; injection volume: approx. 550 μl; number of injections: 1). The product containing fractions are combined and concentrated in vacuo.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialAfter drying with magnesium sulfate
  3. customthe solvent is evaporated off in vacuo
  4. filtrationThen the reaction mixture is filtered
  5. custompurified by preparative HPLC (column: Nucleosil 100-5 C 18 Nautilus 20 mm×50 mm, 5 μm; solvent A: acetonitrile, solvent B: water+0.1% formic acid; gradient: 0 min 10% A, 2 min 10% A, 6 min 90% A, 7 min 90% A, 7.1 min 10% A, 8 min 10% A; wavelength: 220 nm; injection volume: approx. 550 μl; number of injections: 1)
  6. additionThe product containing fractions
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-97365a0212ad40b69b34b75a28e5d97b
Source dataset
uspto-grants-2007_06
Patent number
US07230017B2

Reaction notes

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