Methanol → Diethylamine

HRID 869719Notes

Reaction equation

HRID 869719 reaction equation
[N:1]1([C:6]2[CH:11]=[C:10]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:9]3[N:19]=[C:20]([C:22](=[O:26])[C:23](=[O:25])[CH3:24])[CH:21]=[C:8]3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][C:33]=1[NH2:34].[CH3:35]O>O>[CH2:2]([NH:1][CH2:5][CH3:4])[CH3:3].[CH3:23][C:22]1([C:20]2[CH:21]=[C:8]3[N:7]=[C:6]([N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:11]=[C:10]([NH:12][CH:13]4[CH2:14][CH2:15][O:16][CH2:17][CH2:18]4)[N:9]3[N:19]=2)[N:27]=[C:28]2[CH:29]=[N:30][CH:31]=[CH:32][C:33]2=[N:34][CH2:35]1.[N:1]1([C:6]2[CH:11]=[C:10]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)[N:9]3[N:19]=[C:20]([C:22](=[O:26])[C:23](=[O:25])[CH3:24])[CH:21]=[C:8]3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 887MethanolHCID 59183,4-DiaminopyridineHCID 67394792HCID 67394792, compound

Product 3

HCID 8021DiethylamineHCID 67394792HCID 67394792, compoundHCID 67406253HCID 67406253, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1-[5-pyrrolidin-1-yl-7-(tetrahydro-2H-pyran-4-ylamino)-pyrazolo[1,5-a]pyrimidin-2-yl]propane-1,2-dione (87 mg, 0.243 mmol) in methanol (3 mL) and water (0.3 mL) was added 3,4-diaminopyridine (29 mg, 0.268 mmol) at room temperature. After being stirred for 24 h at same temperature, the reaction mixture was concentrated in vacuo. The crude was purified by silica gel column chromatography (chloroform:methanol=99:1 to 19:1) and HPLC(CHIRALPAK IC, 20Φ×250 mm, hexane:etanol:diethylamine=30:70:0.1, frow rate 5.0 mL/min) to give 2-(3-methylpyrido[3,4-b]pyrazin-3-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (the compound of Example 5.001 listed in the Table of Examples as described hereinafter) as a more polar compound and 2-(2-methylpyrido[3,4-b]pyrazin-2-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine (the compound of Example 5.002 listed in the Table of Examples as described hereinafter) as a less polar compound. The absolute configuration was determined by X-ray analysis of 2-(2-methylpyrido[3,4-b]pyrazin-2-yl)-5-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe crude was purified by silica gel column chromatography (chloroform:methanol=99:1 to 19:1) and HPLC(CHIRALPAK IC, 20Φ×250 mm, hexane

Sources & evidence

ORD record
ord-8948c24df66f4a56b7adb530408b223b
Source dataset
uspto-grants-2015_03
Patent number
US08969376B2

Reaction notes

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