Azetidine → 4-(Azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine

HRID 1907198Notes

Reaction equation

HRID 1907198 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.Cl[C:6]1[C:11]2=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[N:13]=[C:14]([CH3:15])[N:10]2[N:9]=[CH:8][N:7]=1.C(=O)(O)[O-].[Na+].COC(C)(C)C>ClCCl>[N:1]1([C:6]2[C:11]3=[C:12]([C:16]4[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=4)[N:13]=[C:14]([CH3:15])[N:10]3[N:9]=[CH:8][N:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 15413tert-Butyl methyl etherHCID 516892Sodium BicarbonateHCID 866697194-chloro-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine

Product 1

HCID 681820894-(Azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of azetidine (9.21 g, 161 mmol) in dichloromethane (75 mL) was added to a solution of 4-chloro-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine (38.14 g, 153.4 mmol) in dichloromethane (310 mL). After stirring for 5 minutes, the reaction was treated with aqueous sodium bicarbonate solution (0.89 M, 260 mL, 231 mmol) and vigorously stirred for 2 hours. After the phases separated, a white solid was collected by filtration and mixed with water and dichloromethane; it did not completely dissolve. Filtration provided a second water/dichloromethane mixture, which was combined with the original filtrate. The layers were separated, and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (250 mL), then dried over sodium sulfate and filtered. The filtrate was concentrated on a rotary evaporator at 45° C. until solid began to form in the flask. tert-Butyl methyl ether (400 mL) was added with stirring, and the mixture was granulated for 1 hour. Filtration provided the product as a white solid. Yield: 36.07 g, 133.9 mmol, 87%. 1H NMR (400 MHz, CDCl3) δ 2.23-2.31 (m, 2H), 2.65 (s, 3H), 3.97 (s, 3H), 3.98-4.08 (m, 4H), 7.61 (s, 1H), 7.62 (s, 1H), 7.85 (s, 1H).

Workup

  1. stirringvigorously stirred for 2 hours
  2. customAfter the phases separated
  3. filtrationa white solid was collected by filtration
  4. additionmixed with water and dichloromethane
  5. dissolutionit did not completely dissolve
  6. filtrationFiltration
  7. customprovided a second water/dichloromethane mixture, which
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with dichloromethane (3×100 mL)
  10. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (250 mL)
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated on a rotary evaporator at 45° C. until solid
  14. customto form in the flask
  15. stirringwith stirring
  16. waitthe mixture was granulated for 1 hour
  17. filtrationFiltration

Sources & evidence

ORD record
ord-0c66de089f4747c3a028de4bfd244ec4
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Reaction notes

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