Triethylamine → Methyl 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate

HRID 346533Notes

Reaction equation

HRID 346533 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]([NH2:16])=[NH:15])=[N:6]1.[C:21](/[C:23](/[N:26]([C:28]([O:30][CH3:31])=[O:29])[CH3:27])=[CH:24]\[O-])#[N:22].[Na+].C(N(CC)CC)C>C1(C)C=CC=CC=1>[NH2:22][C:21]1[C:23]([N:26]([CH3:27])[C:28](=[O:29])[O:30][CH3:31])=[CH:24][N:16]=[C:14]([C:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[N:5]([CH2:4][C:3]3[CH:17]=[CH:18][CH:19]=[CH:20][C:2]=3[F:1])[N:6]=2)[N:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 114039861-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamideHCID 57469797Sodium (E)-2-cyano-2-[(methoxycarbonyl)(methyl)amino]ethenolate

Product 1

HCID 12114048Methyl 4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Under argon, 0.80 g (2.61 mmol) of 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxamidine from Example 6A, 0.51 g (2.86 mmol) of sodium (E)-2-cyano-2-[(methoxycarbonyl)(methyl)amino]ethenolate from Example 10A and 0.53 g (0.73 ml, 5.23 mmol) of triethylamine are added to 50 ml of toluene. The mixture is heated under reflux for 9 hours. It is then cooled to RT again and is mixed and extracted with dichloromethane and water. The organic phase is dried over magnesium sulphate, filtered and concentrated in vacuo in a rotary evaporator. The residue is mixed with 5 ml of diethyl ether and crystallizes therewith. The crystals are filtered off with suction, dried and purified by preparative RP-HPLC.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 9 hours
  3. additionis mixed
  4. extractionextracted with dichloromethane and water
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo in a rotary evaporator
  8. additionThe residue is mixed with 5 ml of diethyl ether
  9. customcrystallizes
  10. filtrationThe crystals are filtered off with suction
  11. customdried
  12. custompurified by preparative RP-HPLC

Sources & evidence

ORD record
ord-a00e7375585f4cfb8f1e9a361360ea54
Source dataset
uspto-grants-2007_02
Patent number
US07173037B2

Reaction notes

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