Acetic Acid → [4-(3-Pyridylmethylamino)-2-(2-methylphenyl)benzoyl]methionine methyl ester

HRID 2121237Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:26])[C@H:4]([CH2:22][CH2:23][S:24][CH3:25])[NH:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20].[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH:33]=O)[CH:28]=1.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH3:1][O:2][C:3](=[O:26])[C@H:4]([CH2:22][CH2:23][S:24][CH3:25])[NH:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH2:33][C:29]2[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=2)=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20]

Participants

Conditions

Temperature: 25 °C

Procedure

The aniline prepared in Example 308C (180 mg, 0.48 mmol) and 3-pyridine carboxaldehyde (55 mg, 0.51 mmol) were combined in methanol (4 mL) and sodium cyanoborohydride (48 mg, 0.77 mmol) was added followed by 100 mg of crushed molecular sieves. The reaction was adjusted to pH6 with acetic acid and stirred at 25° C. for 3 hours. The reaction was concentrated and transferred directly to a column of silica gel and purified by flash chromatography (5% methanol-ethyl acetate) to give the tide compound (182 mg, 82%) as an oil that solidified after standing. 1H NMR (300 MHz, CD3OD) δ 8.54 (d, J=2.4 Hz, 1H), 8.40 (dd, J=5.1, 1.3 Hz, 1H), 7.84 (bd, J=8.4 Hz, 1H), 7.65-7.55 (m, 1H), 7.40 (dd, J=7.8, 4.7 Hz, 1H), 7.30-7.10 (m, 4H), 6.66 (dd, J=8.8, 2.3 Hz, 1H), 6.37 (d, J=2.3 Hz, 1H), 4.45 (s, 2H), 3.64 (s, 3H), 2.10-1.98 (m, 8H), 1.90-1.78 (m, 1H), 1.65-1.55 (m, 1H). MS (CI) 464 (M+H)+. HRMS FAB Calcd m/z MH+ for C26H29O3N3S 464.2008, found 464.2023.

Workup

concentrationThe reaction was concentrated
custompurified by flash chromatography (5% methanol-ethyl acetate)

Sources & evidence

ORD record: ord-50270b77adbb41ce88ad62d36f627cd6
Source dataset: uspto-grants-2004_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06693123B2

Reaction notes

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