Sodium bis(2-methoxyethoxy)aluminiumhydride → N-{4-[2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-(hydroxymethyl)-4-pyridinyl]-2-hydroxyphenyl}acetamide

HRID 2218269Notes

Reaction equation

HRID 2218269 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:16]([C:17](OC(C)(C)C)=[O:18])=[C:15]([NH2:24])[N:14]=[C:13]([C:25]3[C:30]([O:31][CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)=[CH:29][CH:28]=[CH:27][C:26]=3[O:41][CH2:42][CH:43]3[CH2:45][CH2:44]3)[CH:12]=2)=[CH:7][C:6]=1[OH:46])(=[O:3])[CH3:2].[H-].COCCO[Al+]OCCOC.[Na+].[H-]>C1COCC1>[NH2:24][C:15]1[C:16]([CH2:17][OH:18])=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[C:6]([OH:46])[CH:7]=2)[CH:12]=[C:13]([C:25]2[C:30]([O:31][CH2:32][C:33]3[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=3)=[CH:29][CH:28]=[CH:27][C:26]=2[O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[N:14]=1

Participants

4

Reactant 2

HCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 69147614HCID 69147614, compound

Product 1

HCID 69144971N-{4-[2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-(hydroxymethyl)-4-pyridinyl]-2-hydroxyphenyl}acetamideYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (0° C.) solution of tert-butyl 4-[4-(acetylamino)-3-hydroxyphenyl]-2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}nicotinate (1.65 g, 2.64 mmol) in THF (25.0 mL) under argon atmosphere was added a solution of sodium bis(2-methoxyethoxy)aluminum hydride (3.7 N in toluene, 4.12 mL, 21.1 mmol) in THF (3 mL) dropwise. After being stirred for 30 minutes, the mixture was quenched with ethyl acetate and poured into saturated aqueous sodium potassium tartarate. The extracted organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol, 19:1-9:1) to give N-{4-[2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-(hydroxymethyl)-4-pyridinyl]-2-hydroxyphenyl}acetamide (0.48 g, 33%); LC-MS (m/z=556, M+1).

Workup

  1. customthe mixture was quenched with ethyl acetate
  2. additionpoured into saturated aqueous sodium potassium tartarate
  3. washThe extracted organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (dichloromethane:methanol, 19:1-9:1)

Sources & evidence

ORD record
ord-0d8e354ec74341b0b948feb5b6fd46a4
Source dataset
uspto-grants-2008_08
Patent number
US07410986B2

Reaction notes

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