Acetonitrile → (3S)-1-(3-benzyl-5-tert-butyl-triazolo[4,5-d]pyrimidin-7-yl)pyrrolidin-3-ol

HRID 400975Notes

Reaction equation

HRID 400975 reaction equation
[CH2:1]([N:8]1[C:12]2[N:13]=[C:14]([C:18]([CH3:21])([CH3:20])[CH3:19])[N:15]=[C:16](Cl)[C:11]=2[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(#N)C.C(N(C(C)C)C(C)C)C.[NH:34]1[CH2:38][CH2:37][C@H:36]([OH:39])[CH2:35]1>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[C:12]2[N:13]=[C:14]([C:18]([CH3:21])([CH3:20])[CH3:19])[N:15]=[C:16]([N:34]3[CH2:38][CH2:37][C@H:36]([OH:39])[CH2:35]3)[C:11]=2[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 2733874(3S)-pyrrolidin-3-olHCID 866833853-Benzyl-5-tert-butyl-7-chloro-triazolo[4,5-d]pyrimidine

Product 1

HCID 86683384(3S)-1-(3-benzyl-5-tert-butyl-triazolo[4,5-d]pyrimidin-7-yl)pyrrolidin-3-olYield 96.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3-benzyl-5-tert-butyl-7-chloro-3H-[1,2,3]triazolo[4,5-d]pyrimidine (192.2 g, 548 mmol, Eq: 1.00) was charged in the reactor followed by Acetonitrile (780 g, 1.0 l) and N-Ethyldiisopropylamine (108 g, 143 ml, 822 mmol, Eq: 1.5). (S)-Pyrrolidin-3-ol (54.1 g, 51.6 ml, 603 mmol, Eq: 1.1) was added dropwise over 30 min at Tr=20 to <30° C. After 2 h at 25° C., the reaction mixture was transferred with Toluene (865 g, 1.0 l) into a 3 l round bottom flask and it was concentrated on a rotary evaporator, to switch solvent to toluene. The toluene solution was washed with a 10% aqueous citric acid solution (1.0 l). The aqueous phase was separated and extracted with toluene (434 g, 500 ml). The org. phases were washed sequentially with half saturated aqueous NaHCO3 (500 ml) and half saturated aqueous NaCl (500 ml). The org. phases were combined, dried over MgSO4 and concentrated at 45° C. to ca 500 mL. Heptane (684 g, 1.0 l) was added under stirring. After 5-10 min the product started to crystallize. The white suspension was stirred for 2 h at RT and was filtered. The white filter cake was washed with heptane (274 g, 400 ml) and dried at 45° C./5 mbar to give 186.9 g of the title compound as a white powder. MS (m/e): 353.1 (MH+).

Workup

  1. concentrationit was concentrated on a rotary evaporator
  2. washThe toluene solution was washed with a 10% aqueous citric acid solution (1.0 l)
  3. customThe aqueous phase was separated
  4. extractionextracted with toluene (434 g, 500 ml)
  5. washphases were washed sequentially with half saturated aqueous NaHCO3 (500 ml) and half saturated aqueous NaCl (500 ml)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated at 45° C. to ca 500 mL
  8. additionHeptane (684 g, 1.0 l) was added
  9. waitAfter 5-10 min the product started
  10. customto crystallize
  11. stirringThe white suspension was stirred for 2 h at RT
  12. filtrationwas filtered
  13. washThe white filter cake was washed with heptane (274 g, 400 ml)
  14. customdried at 45° C./5 mbar

Sources & evidence

ORD record
ord-dad8327e5b0c4052b092097eb38ee714
Source dataset
uspto-grants-2014_06
Patent number
US08741906B2

Reaction notes

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