N,N-Dimethylglycine → Rac-1-[3-(4-amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)tetrahydro-1h-1-pyrrolyl]-2-(dimethylamino)-1-ethanone

HRID 897941Notes

Reaction equation

HRID 897941 reaction equation
Cl.[I:2][C:3]1[C:11]2[C:6](=[N:7][CH:8]=[N:9][C:10]=2[NH2:12])[N:5]([CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[N:4]=1.[CH3:18][N:19]([CH3:24])[CH2:20][C:21](O)=[O:22].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl.O>[NH2:12][C:10]1[N:9]=[CH:8][N:7]=[C:6]2[N:5]([CH:13]3[CH2:17][CH2:16][N:15]([C:21](=[O:22])[CH2:20][N:19]([CH3:24])[CH3:18])[CH2:14]3)[N:4]=[C:3]([I:2])[C:11]=12

Participants

8

Reactant 5

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 223473313-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

Product 1

HCID 69203801Rac-1-[3-(4-amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)tetrahydro-1h-1-pyrrolyl]-2-(dimethylamino)-1-ethanoneYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of rac-3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine monohydrochloride (0.367 g, 1.00 mmol) in dichloromethane (10 mL) was added 2-(dimethylamino)acetic acid (0.134 g, 1.30 mmol), 1-hydroxy-7-azabenzotriazole (0.150 g, 1.10 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.249 g, 1.30 mmol), and diisopropylethyl amine (0.65 g, 0.87 mL, 5.0 mmol). The reaction mixture stirred at room temperature for 18 h and was then poured into water (10 mL). The organic phase was separated and washed with brine (10 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to afford rac-1-[3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)tetrahydro-1H-1-pyrrolyl]-2-(dimethylamino)-1-ethanone as a yellow-orange solid (0.278 g, 67%) which was used in subsequent reactions without further purification. RP-HPLC Rt 4.881 min, 80% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 mn; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); m/z 416 (MH+).

Workup

  1. customThe organic phase was separated
  2. washwashed with brine (10 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-66a23be02e044520af40d3da3525d53c
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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