Glycolaldehyde → 2-(6-Amino-5-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamino)-ethanol

HRID 78274Notes

Reaction equation

HRID 78274 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.[OH:29][CH2:30][CH:31]=O.N1C=CC=CC=1C.B.C(=O)([O-])O.[Na+]>C(O)(=O)C.CN(C)C=O>[NH2:28][C:22]1[N:23]=[C:24]([NH:27][CH2:31][CH2:30][OH:29])[CH:25]=[CH:26][C:21]=1[C:19]1[O:18][N:17]=[C:16]([CH2:15][C:12]2[CH:13]=[N:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)[CH:20]=1

Participants

7

Reactant 4

HCID 756GlycolaldehydeHCID 516892Sodium BicarbonateHCID 16217944Borane;2-methylpyridineHCID 441596033-(3-(6-Benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridine-2,6-diamine

Product 1

HCID 592553762-(6-Amino-5-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamino)-ethanolYield 10%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2,6-diamine (40 mg, 0.11 mmol) described in Example 25 and N,N-dimethylformamide (0.5 mL) were 2-hydroxyacetaldehyde (7.7 mg, 0.13 mmol), α-picoline-borane (14 mg, 0.13 mmol), and acetic acid (40 mL) at room temperature, which was stirred for 100 minutes 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 NH silica gel column chromatography (ethyl acetate: methanol=50:1) to obtain the title compound (4.5 mg, 10%).

Workup

  1. customat room temperature
  2. extractionwas extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationafter which the organic layer was concentrated under a reduced pressure
  6. customThe residue thus obtained
  7. customwas purified by reverse-phase high performance liquid chromatography (
  8. additioncontaining 0.1% trifluoroacetic acid)
  9. customto obtain a crude product
  10. custompurified by NH silica gel column chromatography (ethyl acetate: methanol=50:1)

Sources & evidence

ORD record
ord-bdd158e0695d4dd1a3723801b35573b7
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

Loading…