1,2-Dichloroethane → 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

HRID 662104

Reaction equation

HRID 662104 reaction equation
[NH2:1][CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[N:23]1[C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=[CH:25][C:24]=1[C:32]([OH:34])=[O:33].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[CH2:14]([N:11]1[C:6]2=[N:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:2][NH:1][C:29]([C:28]3[N:23]=[C:24]([C:32]([OH:34])=[O:33])[CH:25]=[CH:26][CH:27]=3)=[O:30])[C:4]([NH:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[C:5]2[CH:13]=[N:12]1)[CH3:15]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 103672,6-Pyridinedicarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

Product 1

HCID 578193746-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a third alternate process for preparing the above named compound, 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (0.1 mmol) and 2,6-pyridinedicarboxylic acid (0.1 mmol) was dissolved in DCM (3 mL), and HOBt was added (1.0 eq, 14.0 mg) along with EDC (1.0 eq, 19.0 mg). The resultant solution was stirred overnight. The solution was purified by preparative HPLC (Gilson) to yield 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylic acid. This compound was dissolved in 3 mL of DCM along with 1,1-dimethylethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (41.3 mg, 0.1 mmol), followed by the addition of HOBt (1.0 eq, 14.0 mg) and EDC (1.0 eq, 19.0 mg). The resultant solution was stirred overnight and product was purified by preparative HPLC (Gilson) to give 1,1-dimethylethyl (2S)-4-[(5′-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate. This compound was then dissolved in 2 mL of dioxane:MeOH (3:1). Three drops of HCl (concentrated) were added to the resultant solution and it was heated at 60° C. for 1 h. The solution was applied to the amine column, rinsed with 10 mL of dioxane:MeOH (3:1) to afford 2.2 mg (2.9%) of the above named product. LC-MS m/z 749 (M+H)+, 1.32 min (ret time).

Workup

  1. customIn a third alternate process for preparing the
  2. customThe solution was purified by preparative HPLC (Gilson)

Sources & evidence

ORD record
ord-f70ab161b1df43839ea4248f8ce95a5b
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Linked notes

Loading…