Ethyl oxoacetate → (6-Amino-5-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamino)-acetic acid ethyl ester

HRID 78276Notes

Reaction equation

HRID 78276 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.[CH2:29]([O:31][C:32](=[O:35])[CH:33]=O)[CH3:30].N1C=CC=CC=1C.B.C(=O)([O-])O.[Na+]>C(O)(=O)C.CN(C)C=O>[CH2:29]([O:31][C:32](=[O:35])[CH2:33][NH:27][C:24]1[CH:25]=[CH:26][C:21]([C:19]2[O:18][N:17]=[C:16]([CH2:15][C:12]3[CH:13]=[N:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][CH:11]=3)[CH:20]=2)=[C:22]([NH2:28])[N:23]=1)[CH3:30]

Participants

7

Reactant 4

HCID 70211Ethyl oxoacetateHCID 516892Sodium BicarbonateHCID 16217944Borane;2-methylpyridineHCID 441596033-(3-(6-Benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridine-2,6-diamine

Product 1

HCID 59255333(6-Amino-5-(3-(6-benzyloxy-pyridin-3-ylmethyl)-isoxazol-5-yl)-pyridin-2-ylamino)-acetic acid ethyl esterYield 8%

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 added glyoxylic acid ethyl ester polymer foam (16 mg, 0.16 mmol), α-picoline-borane (14 mg, 0.13 mmol), and acetic acid (40 mL), 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 the title compound (4.9 mg, 8%) as a trifluoroacetic acid salt.

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)

Sources & evidence

ORD record
ord-2666d905fec941479be9c0ba4d2091b4
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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