Sodium hydride → Dichloromethane methanol ammonium hydroxide

HRID 405960Notes

Reaction equation

HRID 405960 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.[H-].[Na+].[ClH:14].[Cl:15][CH2:16][C:17]1[N:18]=[C:19]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:20]2[C:21](=[O:30])[C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=1>CN(C=O)C>[CH2:16]([Cl:15])[Cl:14].[CH3:21][OH:30].[NH4+:3].[OH-:30].[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:16][C:17]3[N:18]=[C:19]4[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:20]4[C:21](=[O:30])[C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[N:3]=[C:2]([I:1])[C:10]=12

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 668313822-(chloromethyl)-3-(3-fluorophenyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochlorideHCID 178508725HCID 178508725, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 25096031HCID 25096031, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.6560 g, 2.513 mmol) in 10 mL of DMF was added sodium hydride, 60% dispersion in mineral oil (0.2010 g, 5.026 mmol) at 0° C. and the mixture was stirred at rt. After 10 min the mixture was added to a solution of 2-(chloromethyl)-3-(3-fluorophenyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one hydrochloride (0.8524 g, 2.513 mmol) in 5 mL of DMF and the resulting mixture was stirred at rt. After 3 h, the mixture was poured into ice-water (100 mL), the resulting precipitate was collected by filtration and washed with water (100 mL) to give a light yellow solid. The light yellow solid was purified by column chromatography on a 40 g Redi-Sep™ column using 0% to 100% gradient of DCM:MeOH:NH4OH (89:9:1) in DCM over 14 min and then 100% isocratic of DCM:MeOH:NH4OH (89:9:1) for 6 min as eluent to give the desired product as a light yellow solid. The light yellow solid was suspended in EtOAc and filtered to give 2-((4-amino-3-iodo-1H-pyrazolo-[3,4-d]pyrimidin-1-yl)methyl)-3-(3-fluorophenyl)-6-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.12 (1 H, s), 7.63 (1 H, dd, J=8.8, 6.8 Hz), 7.27-7.37 (1 H, m), 7.22 (1 H, dd, J=9.0, 0.8 Hz), 7.08-7.16 (2 H, m), 7.00-7.07 (1 H, m), 6.92-6.98 (1 H, m), 5.34 (2 H, s), 2.90 (3 H, s); Mass Spectrum (ESI) m/e=527.8 (M+1).

Workup

  1. stirringthe resulting mixture was stirred at rt
  2. filtrationthe resulting precipitate was collected by filtration
  3. washwashed with water (100 mL)
  4. customto give a light yellow solid
  5. customThe light yellow solid was purified by column chromatography on a 40 g Redi-Sep™ column
  6. customover 14 min

Sources & evidence

ORD record
ord-37120c1060244586b3ff790862f06d58
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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