Formaldehyde → 3-(3-(6-Benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-N6-methyl-pyridin-2,6-diamine

HRID 640557Notes

Reaction equation

HRID 640557 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([CH2:15][C:16]2[CH:20]=[C:19]([C:21]3[C:22]([NH2:28])=[N:23][C:24]([NH2:27])=[CH:25][CH:26]=3)[O:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.N1C=CC=C[C:32]=1C.B.C(=O)([O-])O.[Na+]>C(O)(=O)C.CN(C)C=O>[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([CH2:15][C:16]2[CH:20]=[C:19]([C:21]3[C:22]([NH2:28])=[N:23][C:24]([NH:27][CH3:32])=[CH:25][CH:26]=3)[O:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 16217944Borane;2-methylpyridineHCID 441596033-(3-(6-Benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridine-2,6-diamine

Product 1

HCID 592555243-(3-(6-Benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-N6-methyl-pyridin-2,6-diamineYield 4.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridine-2,6-diamine (50 mg, 0.13 mmol) described in Example 25 and N,N-dimethylformamide (0.5 mL) were added a formaldehyde aqueous solution (14 mg, 0.17 mmol, content: 37%), α-picoline-borane (17 mg, 0.16 mmol), and acetic acid (50 μL) at room temperature, which was stirred overnight at the same temperature. A saturated sodium hydrogencarbonate aqueous solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, after which the organic layer was concentrated under a reduced pressure. The residue thus obtained was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) to obtain a crude product, and then purified by silica gel thin-layer chromatography (diethyl ether:hexane=2:1) to obtain the title compound (2.3 mg, 4.4%).

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationafter which the organic layer was concentrated under a reduced pressure
  5. customThe residue thus obtained
  6. customwas purified by reverse-phase high performance liquid chromatography (
  7. additioncontaining 0.1% trifluoroacetic acid)
  8. customto obtain a crude product
  9. custompurified by silica gel thin-layer chromatography (diethyl ether:hexane=2:1)

Sources & evidence

ORD record
ord-44ecabe9be3e44cca9cf92bd41968f7e
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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