Tetrahydrofuran → 2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(2-hydroxymethyl-4-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide

HRID 2387739Notes

Reaction equation

HRID 2387739 reaction equation
[Si]([O:8][CH2:9][Sn](CCCC)(CCCC)CCCC)(C(C)(C)C)(C)C.[CH3:23][N:24]1[CH2:28][CH2:27][CH2:26][C:25]1=O.ClC1N=C(C)C(OC[C:40]2([C:50]([NH:52][C:53]3[CH:58]=[CH:57][C:56]([F:59])=[CH:55][N:54]=3)=[O:51])[CH2:42][CH:41]2[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=2)=CN=1.[F-].C([N+:65](CCCC)(CCCC)CCCC)CCC.C1[CH2:82][O:81]CC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:49][C:45]1[CH:44]=[C:43]([C:41]2([CH2:82][O:81][C:27]3[C:26]([CH3:25])=[N:65][C:23]([CH2:9][OH:8])=[N:24][CH:28]=3)[CH2:42][CH:40]2[C:50]([NH:52][C:53]2[CH:58]=[CH:57][C:56]([F:59])=[CH:55][N:54]=2)=[O:51])[CH:48]=[CH:47][CH:46]=1

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 13387N-methyl-2-pyrrolidoneHCID 2724141Tetrabutylammonium FluorideHCID 14270862Tert-butyl-dimethyl-(tributylstannylmethoxy)silaneHCID 86664273([(2-chloro-4-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 764691762-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(2-hydroxymethyl-4-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

(Tert-butyldimethylsilyloxymethyl)tri-n-butyltin (Tetrahedron Vol. 45, No. 4, 993-1006: 121 mg) and tetrakistriphenylphosphinepalladium (13.4 mg) were added to a N-methylpyrrolidone (2.5 ml) solution of the compound 323-4 (100 mg), and the obtained mixture was stirred at 140° C. for 6 hours. The temperature of the reaction solution was returned to room temperature. Thereafter, THF (2 ml) and tetrabutyl ammonium fluoride (1 M THF solution: 232 ul) were added to the reaction solution, and the obtained mixture was stirred at room temperature for 14 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=19:1 to 1:1), so as to obtain the title compound (26.6 mg).

Workup

  1. customwas returned to room temperature
  2. stirringthe obtained mixture was stirred at room temperature for 14 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (n-heptane:ethyl acetate=19:1 to 1:1)

Sources & evidence

ORD record
ord-d9b2559dd97742eca766a3777d0d9e48
Source dataset
uspto-grants-2012_09
Patent number
US08268848B2

Reaction notes

Loading…