Diisopropylethylamine → 2-{[(3-tert-Butoxycarbonylamino-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester

HRID 251237Notes

Reaction equation

HRID 251237 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][C:8]1[C:9]([CH2:14][NH:15][CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)=[N:10][CH:11]=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:25][O:26][C:27](=[O:38])[C:28]1[CH:33]=[C:32]([C:34]#[N:35])[CH:31]=[CH:30][C:29]=1[CH2:36]Br.CCN(C(C)C)C(C)C>CC#N>[CH3:25][O:26][C:27](=[O:38])[C:28]1[CH:33]=[C:32]([C:34]#[N:35])[CH:31]=[CH:30][C:29]=1[CH2:36][N:15]([CH2:14][C:9]1[C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:24])=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:16][C:17]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 17965928Methyl 2-(bromomethyl)-5-cyanobenzoateHCID 67271562(2-{[(3-Methyl-pyridin-2-ylmethyl)-amino]-methyl}-pyridin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 672728132-{[(3-tert-Butoxycarbonylamino-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-5-cyano-benzoic acid methyl esterYield 90.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Using General Procedure A: A solution (2-{[(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-pyridin-3-yl)-carbamic acid tert-butyl ester (0.220 g, 0.65 mmol), 2-bromomethyl-5-cyano-benzoic acid methyl ester (0.245 g, 0.97 mmol), and DIPEA (0.23 mL, 1.32 mmol) in CH3CN (7 mL) was stirred at room temperature for 21 hours. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 0.294 g (88%) of 2-{[(3-tert-Butoxycarbonylamino-pyridin-2-ylmethyl)-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-5-cyano-benzoic acid methyl ester as a colorless oil. 1H NMR (CDCl3) δ 1.58 (s, 9H), 2.20 (s, 3H), 3.76 (s, 2H), 3.86 (s, 3H), 4.05 (s, 2H), 4.09 (s, 2H), 7.09-7.16 (m, 2H), 7.44 (d, 1H, J=7.8 Hz), 7.55 (dd, 1H, J=8.1, 1.5 Hz), 7.89 (d, 1H, J=8.1 Hz), 8.04 (d, 1H, J=1.5 Hz), 8.09 (dd, 1H, J=1.5, 4.8 Hz), 8.51 (d, 1H, J=7.8 Hz), 8.63 (d, 1H, J=4.8 Hz).

Workup

  1. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-022e0ba79e874dd59c11d3aa0f14874f
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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