1-Hydroxybenzotriazole → N-(4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-oxopyrrolidine-3-carboxamide

HRID 2241246Notes

Reaction equation

HRID 2241246 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([CH3:26])=[N:9]2)=[CH:5][CH:4]=1.[O:29]=[C:30]1[CH:34]([C:35](O)=[O:36])[CH2:33][CH2:32][NH:31]1.Cl.C(N=C=NCCCN(C)C)C.N1(O)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:35]([CH:34]5[CH2:33][CH2:32][NH:31][C:30]5=[O:29])=[O:36])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([CH3:26])=[N:9]2)=[CH:27][CH:28]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 134743702-Oxopyrrolidine-3-carboxylic acidHCID 685133074-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

Product 1

HCID 68514543N-(4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-oxopyrrolidine-3-carboxamideYield 86.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 100 mL round-bottomed flask was charged with 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (20.0 mg, 0.053 mmol; obtained from Example 5, Step D), 2-oxopyrrolidine-3-carboxylic acid (34.1 mg, 0.26 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (50.7 mg, 0.26 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (35.7 mg, 0.26 mmol), N-ethyl-N-isopropylpropan-2-amine (34.2 mg, 0.26 mmol), and THF (10 mL). The reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (2 days). Water (10 mL) was added and extracted with CH2Cl2 (3×50 mL). The organic layers were combined, dried over Na2SO4 and concentrated. The residue purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford the desired product (22.3 mg, 86.2%). LRMS (APCI neg) m/e 488 (M−1).

Workup

  1. customhad been consumed (2 days)
  2. additionWater (10 mL) was added
  3. extractionextracted with CH2Cl2 (3×50 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1

Sources & evidence

ORD record
ord-a81658ad57bf42b98b9d50a0b9734ae4
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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