Ammonia → HCID 89690930, compound

HRID 2278840Notes

Reaction equation

HRID 2278840 reaction equation
Cl[C:2]1[N:3]=[C:4]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[N:10]=2)[N:5]=[N:6][C:7]=1[Cl:8].[NH3:26]>C1COCC1.C(O)C>[Cl:8][C:7]1[N:6]=[N:5][C:4]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[N:10]=2)=[N:3][C:2]=1[NH2:26]

Participants

5

Reactant 2

HCID 222Ammonia4×HCID 89694914HCID 89694914, compound

Product 1

HCID 89690930HCID 89690930, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent4×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

7.000 g (purity 38%, 7.090 mmol) of 3-(5,6-dichloro-1,2,4-triazin-3-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine in 200 ml of absolute THF were initially introduced. With ice-cooling, 4.254 ml (8.508 mmol) of 2N ammonia solution in ethanol were added and the mixture was stirred for 1 h at 0° C. Again with ice-cooling, 4.254 ml (8.508 mmol) of 2N ammonia solution in ethanol were added and the mixture was stirred for 1.5 h at RT. 30 ml (60.000 mmol) of 2N ammonia solution in ethanol was added and the mixture was stirred for 15 min at RT. The reaction mixture was concentrated on a rotary evaporator, suspended in 100 ml of dichloromethane, admixed with 50 ml (100.00 mmol) of 2N ammonia solution in ethanol and stirred for 2 h at RT. The mixture was concentrated on a rotary evaporator and purified by chromatography on silica gel (mobile phase: dichloromethane/methanol, gradient 20:1→10:1). The product-containing fractions were concentrated and stirred with DMSO. The solid was filtered off with suction, after-washed with acetonitrile and dried under high vacuum. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 20:80→100:0). This gave 1.68 g of the target compound (purity 65%; 43% of theory).

Workup

  1. temperatureWith ice-cooling
  2. temperatureAgain with ice-cooling
  3. stirringthe mixture was stirred for 1.5 h at RT
  4. stirringthe mixture was stirred for 15 min at RT
  5. concentrationThe reaction mixture was concentrated on a rotary evaporator
  6. stirringstirred for 2 h at RT
  7. concentrationThe mixture was concentrated on a rotary evaporator
  8. custompurified by chromatography on silica gel (mobile phase: dichloromethane/methanol, gradient 20:1→10:1)
  9. concentrationThe product-containing fractions were concentrated
  10. stirringstirred with DMSO
  11. filtrationThe solid was filtered off with suction
  12. washafter-washed with acetonitrile
  13. customdried under high vacuum
  14. customThe residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 20:80→100:0)

Sources & evidence

ORD record
ord-706a80037c84462e9c654c5351501078
Source dataset
uspto-grants-2015_09
Patent number
US09133191B2

Reaction notes

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