2,3-Dihydroxybutanedioate → (5-Aminomethyl-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol

HRID 1592655Notes

Reaction equation

HRID 1592655 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][C:5]=1[CH2:12][N:13]([CH2:22][C:23]1[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=1)[CH:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[CH3:15].[H-].[H-].[H-].[H-].[Li+].[Al+3].C(C(C(C([O-])=O)O)O)([O-])=O>C1COCC1>[NH2:11][CH2:10][C:8]1[CH:7]=[CH:6][C:5]([CH2:12][N:13]([CH2:22][C:23]2[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH3:15])=[C:4]([CH2:3][OH:2])[CH:9]=1

Participants

5

Reactant 3

HCID 38061142,3-DihydroxybutanedioateHCID 21226445Aluminium lithium hydrideHCID 672713395-Cyano-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzoic acid methyl ester

Product 1

HCID 58997196(5-Aminomethyl-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanolYield 9.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-cyano-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzoic acid methyl ester (0.88 g, 2.2 mmol) in dry THF (11 mL) under Ar at 0° C. was slowly added 1.0 M LiAlH4 in THF (22 mL, 22.0 mmol). The reaction was stirred at room temperature for 2 hours, then cooled to 0° C. Saturated aqueous KNa Tartrate (Rochelle's salt, 30 mL) was slowly added, and the phases were separated. The aqueous phase was extracted with THF (1×35 mL), and the organic extract was dried (MgSO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) followed by radial chromatography twice on silica gel (33:1:1 and 50:1:1 CH2Cl2-MeOH—NH4OH respectively) provided 75.1 mg (9%) of COMPOUND 394 as a white solid. 1H NMR (CDCl3) δ 1.56 (d, 6H, J=6.9 Hz), 2.04 (s, 3H), 3.66-3.98 (m, 6H), 4.05-4.12 (m, 1H), 4.26 (s, 2H), 7.04-7.08 (m, 1H), 7.14-7.23 (m, 3H), 7.27-7.28 (m, 1H), 7.34-7.39 (m, 2H), 7.63-7.69 (m, 1H), 8.39 (d, 1H, J=4.5 Hz), 8.58 (d, 1H, J=4.5 Hz). 13C NMR (CDCl3) δ 11.85, 18.43, 46.48, 52.54, 53.97, 58.89, 63.56, 122.53, 122.60, 124.15, 126.40, 130.15, 131.98, 132.93, 135.93, 136.65, 138.51, 142.48, 143.57, 146.57, 148.92, 156.73, 161.25. ES-MS m/z 377 (M+H). Anal. Calcd. for C23H28N4O.0.1H2O.0.3CH2Cl2: C, 69.31; H, 7.19; N, 13.88. Found: C, 69.56; H, 7.27; N, 13.70.

Workup

  1. customat 0° C.
  2. temperaturecooled to 0° C
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with THF (1×35 mL)
  5. extractionthe organic extract
  6. dry with materialwas dried (MgSO4)
  7. concentrationconcentrated
  8. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-376a43ee33ea4a179b48474c5aa0076e
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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