Trifluoroacetic acid → HCID 178441800, compound

HRID 705134Notes

Reaction equation

HRID 705134 reaction equation
C(N(CC)CC)C.Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[C:20]2[N:21]=[C:22]([CH2:37][CH2:38][CH2:39][CH3:40])[N:23]=[C:24]([NH:25]CC3C=CC(OC)=CC=3OC)[C:19]=2[NH:18][N:17]=1.[NH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1.FC(F)(F)C(O)=O>C(#N)C>[CH2:37]([C:22]1[N:23]=[C:24]([NH2:25])[C:19]2[NH:18][N:17]=[C:16]([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][N:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)[C:20]=2[N:21]=1)[CH2:38][CH2:39][CH3:40]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8082Piperidine2×HCID 8471Triethylamine2×HCID 178441808HCID 178441808, compound

Product 1

HCID 178441800HCID 178441800, compoundYield 284.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Triethylamine (0.085 mL, 0.608 mmol) was added to a solution of 3-(7-bromoheptyl)-5-butyl-N-(2,4-dimethoxybenzyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine (150 mg, 0.203 mmol) and piperidine (0.060 mL, 0.608 mmol) in anhydrous acetonitrile (7 mL). The solution was stirred at ambient temperature for 1.5 hours. Additional piperidine (0.060 mL, 0.608 mmol) and triethylamine (0.085 mL, 0.608 mmol) were added to the reaction mixture and stirring at ambient temperature was continued for 17 hours. The reaction mixture was evaporated in vacuo to yield a clear oil. The oil was partitioned between ethyl acetate (20 mL) and water/brine (1:1, 5 mL). The organic layer was separated, passed through a hydrophobic frit and evaporated in vacuo to yield a clear oil. The oil was dissolved in trifluoroacetic acid (3 mL, 38.9 mmol) and heated at 60° C. for 3 hours. The reaction mixture was evaporated in-vacuo and the residue was dissolved in 3:1 chloroform:IPA (20 mL) and washed with aqueous sodium hydroxide (0.1M, 5 mL). The organic phase was separated using a hydrophobic frit and the aqueous back extracted with 3:1 chloroform:IPA (20 mL). The combined organic extracts were evaporated in-vacuo to yield a yellow oil (215 mg). The oil was dissolved in MeOH:DMSO (1:1) (3×1 mL) and purified by MDAP (Method B). Appropriate fractions were combined and evaporated in-vacuo to yield a brown oil (88.2 mg). The oil was dissolved in MeOH:DMSO (1:1) (1 mL) and purified by MDAP (Method A). Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a white solid (40.5 mg).

Workup

  1. stirringstirring at ambient temperature
  2. waitwas continued for 17 hours
  3. customThe reaction mixture was evaporated in vacuo
  4. customto yield a clear oil
  5. customThe oil was partitioned between ethyl acetate (20 mL) and water/brine (1:1, 5 mL)
  6. customThe organic layer was separated
  7. customevaporated in vacuo
  8. customto yield a clear oil
  9. temperatureheated at 60° C. for 3 hours
  10. customThe reaction mixture was evaporated in-vacuo
  11. dissolutionthe residue was dissolved in 3:1 chloroform
  12. washIPA (20 mL) and washed with aqueous sodium hydroxide (0.1M, 5 mL)
  13. customThe organic phase was separated
  14. extractionthe aqueous back extracted with 3:1 chloroform
  15. customThe combined organic extracts were evaporated in-vacuo

Sources & evidence

ORD record
ord-3d2b9ebf0d4b404eb3f4b6a84c976165
Source dataset
uspto-grants-2015_11
Patent number
US09173872B2

Reaction notes

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