Tetrabutylammonium Fluoride → 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-methanol

HRID 717804Notes

Reaction equation

HRID 717804 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([C:14]#[C:15][CH2:16][OH:17])=[CH:4][N:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:14]=[C:15]([CH2:16][OH:17])[N:8]([CH:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866648613-(2-Chloro-4-(cyclopentylamino)-5-pyrimidinyl)-2-propyn-1-ol

Product 1

HCID 866935732-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A dry nitrogen-flushed 5 L 4-neck round bottom flask is charged with 100 g (Purity: 98%, 0.389 mol 1.0 eq.) of 3-(2-chloro-4-(cyclopentylamino)pyrimidin-5-yl)prop-2-yn-1-ol, (A1d), 880 g (1000 mL) of peroxide free tetrahydrofuran and 753 g, (856 mL) of tetrabutylammonium fluoride, 1.0M solution in THF. The content is stirred at 25° C. for 10 min, and then the solution is warmed to 60° C. This temperature is maintained for 1.5 h until the starting material, A1d, is ≦2.5±0.5% as determined by HPLC analysis. The resulting solution is cooled to below 30±3° C.2, and distilled under reduced pressure to remove THF. 79 g (100 mL) of 2-propanol is added. The sample is stirred for 15 min and 1000 g (1000 mL) of water then add slowly over 30 min The sample is stirred at 20±3° C. for 30 min and then filtered. The cake is washed twice with 200 g (2×100 mL) of water. The solids are dried at 50° C. for 16 h to afford Compound A1c as a tan, crystalline solid, mp=174-176° C.

Workup

  1. customA dry nitrogen-flushed 5 L 4-neck round bottom flask
  2. temperaturethe solution is warmed to 60° C
  3. temperatureThis temperature is maintained for 1.5 h until the starting material
  4. temperatureThe resulting solution is cooled to below 30±3° C
  5. distillation2, and distilled under reduced pressure
  6. customto remove THF
  7. addition79 g (100 mL) of 2-propanol is added
  8. stirringThe sample is stirred for 15 min
  9. addition1000 g (1000 mL) of water then add slowly over 30 min The sample
  10. stirringis stirred at 20±3° C. for 30 min
  11. filtrationfiltered
  12. washThe cake is washed twice with 200 g (2×100 mL) of water
  13. customThe solids are dried at 50° C. for 16 h
  14. customto afford Compound A1c as a tan, crystalline solid, mp=174-176° C.

Sources & evidence

ORD record
ord-28fb8f5252ea467594e701429422e764
Source dataset
uspto-grants-2015_11
Patent number
US09193732B2

Reaction notes

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