Triethylamine → 1-{2-[6-chloro-8-(3-fluorophenyl)-9-methyl-9H-2-purinyl]-1-ethynyl}-1-cyclopentanol

HRID 1369382Notes

Reaction equation

HRID 1369382 reaction equation
[Cl:1][C:2]1[N:10]=[C:9](I)[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[N:6]2[CH3:12].[C:20]([C:22]1([OH:27])[CH2:26][CH2:25][CH2:24][CH2:23]1)#[CH:21].C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[N:10]=[C:9]([C:21]#[C:20][C:22]2([OH:27])[CH2:26][CH2:25][CH2:24][CH2:23]2)[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1)[N:6]2[CH3:12]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 870741-EthynylcyclopentanolHCID 99522656-chloro-8-(3-fluorophenyl)-2-iodo-9-methyl-9H-purine

Product 1

HCID 105712351-{2-[6-chloro-8-(3-fluorophenyl)-9-methyl-9H-2-purinyl]-1-ethynyl}-1-cyclopentanolYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Chloro-8-(3-fluorophenyl)-2-iodo-9-methyl-9H-purine (1076 g) was dissolved in 10 liters of tetrahydrofuran and 97.2 g of bistriphenylphosphine palladium dichloride, 26.4 g of cuprous iodide and 248 g of 1-ethynylcyclopentanol were added thereto. Into this mixture were added dropwise 331 ml of triethylamine within 15 minutes keeping the bulk temperature at not higher than 26° C. in a nitrogen atmosphere. After reacting at room temperature for 4 hours, the reaction solution was diluted with 10 liters of ethyl acetate and washed with 4 liters of a saturated ammonium chloride solution and 1 liter of brine. The organic layer was dried over 2 kg of anhydrous sodium sulfate and filtered followed by concentrating to an extent of 3 liters. The resulting residue was diluted with 4 liters of hexane-ethyl acetate (1:1), filtered and washed with 1 liter of hexane to give 732 g of 1-{2-[6-chloro-8-(3-fluorophenyl)-9-methyl-9H-2-purinyl]-1-ethynyl}-1-cyclopentanol. The yield was 88%.

Workup

  1. customhigher than 26° C.
  2. washwashed with 4 liters of a saturated ammonium chloride solution and 1 liter of brine
  3. dry with materialThe organic layer was dried over 2 kg of anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationby concentrating to an extent of 3 liters
  6. additionThe resulting residue was diluted with 4 liters of hexane-ethyl acetate (1:1)
  7. filtrationfiltered
  8. washwashed with 1 liter of hexane

Sources & evidence

ORD record
ord-2649143fb6084b078433e265d0f88310
Source dataset
uspto-grants-2003_06
Patent number
US06579868B1

Reaction notes

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