Formaldehyde → 3-iodo-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 2056090Notes

Reaction equation

HRID 2056090 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]2)[N:3]=1.[C:18](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O.[OH-].[Na+]>ClC(Cl)C>[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH3:18])[CH2:13]2)[N:3]=1

Participants

6

Reactant 4

HCID 712Formaldehyde2×HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 223467113-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 223473453-iodo-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 94.8%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a mixture of 3-iodo-1-(3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.4 g, 0.00116 mol) and sodium triacetoxyborohydride (0.34 g, 0.00162 mol) in dichloroethane (30 mL) was added formaldehyde solution (37% in water, 0.035 mL, 0.00128 mol, 1.1 eq.) at room temperature. The mixture was stirred at room temperature under an atmosphere of nitrogen for 18 hours. Additional formaldehyde solution (37% in water, 0.035 mL, 0.00128 mol, 1.1 eq.) was added, and the mixture was stirred at room temperature for 2 hours. A 5 N aqueous solution of sodium hydroxide (5 mL) was added to the mixture. The solvent was removed under the reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (3×150 mL). The combined organic extracts were washed with water, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure, and the mixture was lyophilized to yield 3-iodo-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.41 g, 0.0011 mol). RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-95% acetonitrile—0.1M ammonium acetate over 10 min, 1 mL/min) Rt 6.0 min. MS: MH+ 359

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hours
  2. customThe solvent was removed under the reduced pressure
  3. customThe residue was partitioned between water and dichloromethane
  4. extractionThe aqueous layer was extracted with dichloromethane (3×150 mL)
  5. washThe combined organic extracts were washed with water, and brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvents were evaporated under the reduced pressure

Sources & evidence

ORD record
ord-86b4c795500741b9bba68d099d0b9af5
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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