Triethylamine → 5-((Benzyloxy)methyl)-2-butyl-7-(5-(4-isopropylpiperazin-1-yl)pent-1-yn-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine

HRID 1487255Notes

Reaction equation

HRID 1487255 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17]([NH2:19])=[N:16][C:15]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][C:13]=2[C:12](I)=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:32][CH:33]([N:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH2:42][CH2:43][C:44]#[CH:45])[CH2:37][CH2:36]1)[CH3:34]>CN(C)C=O.CO.CS(C)=O.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17]([NH2:19])=[N:16][C:15]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][C:13]=2[C:12]([C:45]#[C:44][CH2:43][CH2:42][CH2:41][N:38]2[CH2:39][CH2:40][N:35]([CH:33]([CH3:34])[CH3:32])[CH2:36][CH2:37]2)=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 901769325-((Benzyloxy)methyl)-2-butyl-7-iodo-5H-pyrrolo[3,2-d]pyrimidin-4-amineHCID 901770341-iso-Propyl-4-(pent-4-yn-1-yl)piperazine2×

Product 1

HCID 1184538115-((Benzyloxy)methyl)-2-butyl-7-(5-(4-isopropylpiperazin-1-yl)pent-1-yn-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-amineYield 31.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent3×HCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a degassed solution of 5-((benzyloxy)methyl)-2-butyl-7-iodo-5H-pyrrolo[3,2-d]pyrimidin-4-amine (223 mg, 0.511 mmol) in anhydrous N,N-dimethylformamide (3.5 mL) under a nitrogen atmosphere at room temperature was added copper(I) iodide (19 mg, 0.10 mmol), bis(triphenylphosphine)palladium(II)dichloride (40 mg, 0.057 mmol) and finally triethylamine (0.128 mL, 0.920 mmol). The mixture was stirred at room temperature under a nitrogen atmosphere for 10 minutes and then a solution of 1-(1-methylethyl)-4-(4-pentyn-1-yl)piperazine (159 mg, 0.818 mmol) in anhydrous degassed N,N-dimethylformamide (0.5 mL) was added. The reaction mixture was stirred at 55° C. for 40 minutes. A solution of 1-(1-methylethyl)-4-(4-pentyn-1-yl)piperazine 60 mg (0.309 mmol) in anhydrous degassed N,N-dimethylformamide (0.5 mL) was added. The reaction mixture was stirred at 55° C. for 30 minutes. The reaction was evaporated in vacuo to yield a dark yellow oil. The oil was partitioned between water and dichloromethane. The organic layer was separated and the aqueous back extracted with dichloromethane. The combined organic extracts were passed through a hydrophobic frit and evaporated in-vacuo to yield a dark yellow oil. The oil was dissolved in MeOH:DMSO (1:1) (4×1 mL) and purified by MDAP (Method B) Appropriate fractions were combined and evaporated in vacuo to yield the title compound as a yellow oil (80 mg).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at 55° C. for 40 minutes
  3. additionwas added
  4. stirringThe reaction mixture was stirred at 55° C. for 30 minutes
  5. customThe reaction was evaporated in vacuo
  6. customto yield a dark yellow oil
  7. customThe oil was partitioned between water and dichloromethane
  8. customThe organic layer was separated
  9. extractionthe aqueous back extracted with dichloromethane
  10. customevaporated in-vacuo
  11. customto yield a dark yellow oil
  12. custompurified by MDAP (Method B) Appropriate fractions
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-4be3db3f5e244f128211f7edc0429ecc
Source dataset
uspto-grants-2016_08
Patent number
US09428512B2

Reaction notes

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