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

HRID 251255Notes

Reaction equation

HRID 251255 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:17][N:18]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][C:29]=1[C:36](OC)=[O:37])[CH:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[CH3:20])=O)(C)(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].C(C(C(C([O-])=O)O)O)([O-])=O>C1COCC1>[NH2:35][CH2:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][N:18]([CH2:17][C:9]2[NH:8][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]=2)[CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH3:20])=[C:29]([CH2:36][OH:37])[CH:30]=1

Participants

5

Reactant 3

HCID 38061142,3-DihydroxybutanedioateHCID 21226445Aluminium lithium hydrideHCID 672721472-{[(4-Cyano-2-methoxycarbonyl-benzyl)-(1-pyridin-2-yl-ethyl)amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 58997184(5-aminomethyl-2-{[(1H-benzoimidazol-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanolYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-{[(4-cyano-2-methoxycarbonyl-benzyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzoimidazole-1-carboxylic acid tert-butyl ester (0.5065 g, 1.0 mmol) in dry THF (5 mL) under Ar at 0° C. was slowly added 1.0 M LiAlH4 in THF (9.6 mL, 9.6 mmol). The reaction was stirred at room temperature for 3 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 CH2Cl2 (3×35 mL), and the combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (25:1:1 CH2Cl2-MeOH—NH4OH) provided 28.0 mg (7%) of COMPOUND 398 as a white solid. 1H NMR (CDCl3) δ 1.55 (d, 7H), 3.72 (s, 2H), 3.79-3.97 (m, 4H), 4.08-4.15 (m, 1H), 4.61 (s, 2H), 7.00-7.03 (m, 1H), 7.12-7.22 (m, 4H), 7.30-7.34 (m, 2H), 7.39-7.548 (m, 2H), 7.66-7.73 (m, 1H), 8.63 (d, 1H, J=4.3 Hz). 13C NMR (CDCl3) δ 12.64, 46.30, 48.93, 56.11, 60.76, 63.68, 122.24, 122.64, 123.03, 126.86, 130.49, 132.06, 135.86, 137.63, 140.79, 140.79, 143.92, 149.44, 153.77, 161.45. ES-MS m/z 402 (M+H). Anal. Calcd. for C24H27N5O.0.6H2O.0.2CH2Cl2: C, 67.71; H, 6.71; N, 16.31. Found: C, 68.05; H, 6.75; N, 16.38.

Workup

  1. customat 0° C.
  2. temperaturecooled to 0° C
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with CH2Cl2 (3×35 mL)
  5. dry with materialthe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography on silica gel (25:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-bed5a464182048838db2f9983196eeec
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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