Dichloromethane → 4-{[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrile

HRID 251267Notes

Reaction equation

HRID 251267 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]([CH2:23][C:24]1[C:29]([CH3:30])=[CH:28][C:27]([Cl:31])=[CH:26][N:25]=1)[C:14]([CH3:22])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=1)[CH3:15].[Li+].[BH4-].[OH-].[Na+].C(Cl)Cl>CO.C1COCC1>[Cl:31][C:27]1[CH:28]=[C:29]([CH3:30])[C:24]([CH2:23][N:13]([CH2:12][C:5]2[CH:6]=[CH:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[CH2:3][OH:2])[C:14]([CH3:15])([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH3:22])=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 672712132-{[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester

Product 1

HCID 589971284-{[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-3-hydroxymethyl-benzonitrileYield 91.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{[(5-chloro-3-methyl-pyridin-2-ylmethyl)-(1-methyl-1-pyridin-2-yl-ethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester (0.4561 g, 1.0 mmol) in MeOH (5 mL) and THF (5 mL) at 0° C. was added LiBH4. The reaction was stirred at room temperature for 3 hours, then 1N NaOH (25 mL) was added and stirred for 10 minutes. CH2Cl2 (35 mL) was added, the phases were separated, and the aqueous layer was extracted with CH2Cl2 (4×15 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (100:1:1 CH2Cl2-MeOH—NH4OH) provided 0.3847 g (91%) of COMPOUND 404 as a white solid. 1H NMR (CDCl3) δ 1.61 (s, 6H), 2.09 (s, 3H), 3.71 (s, 2H), 3.98 (s, 2H), 4.50-4.51 (m, 2H), 6.39 (s, 1H), 7.09 (1H, J=6.0 Hz), 7.15 (s, 1H), 7.23-7.31 (m, 2H), 7.54-7.58 (m, 2H), 7.65-7.68 (m, 1H), 8.04 (s, 1H), 8.50 (d, 1H, J=3.0 Hz). 13C NMR (CDCl3) δ 18.64, 24.64, 52.42, 53.30, 62.46, 64.46, 111.26, 119.08, 122.35, 122.53, 130.18, 130.98, 131.00, 133.10, 134.03, 136.42, 137.59, 141.71, 144.61, 144.95, 148.30, 155.91, 165.29. ES-MS m/z 422.2 (M+H). Anal. Calcd. for C24H25N4ClO.0.1H2O: C, 68.19; H, 6.01; N, 13.25; Cl, 8.39. Found: C, 68.01; H, 6.04; N, 13.20; Cl, 8.84.

Workup

  1. stirringstirred for 10 minutes
  2. customthe phases were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (4×15 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification of the crude material by column chromatography on silica gel (100:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-e0000acd72704ab48f86b7af60cf0119
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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