Chloroacetaldehyde → [3-(2-Methoxy-1-methyl-ethoxy)-5-phenoxy-pyridine-2-yl]-thiazole-2-yl-amine

HRID 1966241Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH:4]([CH3:23])[O:5][C:6]1[C:7]([NH:19][C:20]([NH2:22])=[S:21])=[N:8][CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=1.Cl[CH2:25][CH:26]=O>CN(C=O)C>[CH3:1][O:2][CH2:3][CH:4]([CH3:23])[O:5][C:6]1[C:7]([NH:19][C:20]2[S:21][CH:25]=[CH:26][N:22]=2)=[N:8][CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=1

Participants

Conditions

Temperature: 100 °C

Procedure

[3-(2-Methoxy-1-methyl-ethoxy)-5-phenoxy-pyridin-2-yl]-thiourea (0.2 mmol) is dissolved in DMF (1 ml) and chloro-acetaldehyde (1.0 eq., 55% in water) is added and stirred three hours at 100° C. After cooling to room temperature the suspension is pored into ice-water and extracted with methyl-tert.-butyl ether. The combined organic phases are washed with brine and dried over MgSO4. The solvent is removed in vacuo. [3-(2-Methoxy-1-methyl-ethoxy)-5-phenoxy-pyridine-2-yl]-thiazole-2-yl-amine (“A28”) is obtained after reversed phase column chromatography (acetonitrile/water+0.1% TFA) as yellow solid in a yield of 46%. HPLC (method C): 1.80 min; LC-MS (method A): 1.72 min, 358.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 7.739 (d, 1H, J=2.3 Hz), 7.477 (d, 1H, J=3.9 Hz), 7.421-7.369 (m, 3H), 7.142-7.087 (m, 2H), 7.025 (d, 2H, J=8 Hz), 5.408 (br, 1H), 4.737-4.696 (m, 1H), 3.639 (dd, 1H, J=6.5 Hz, J=10.6 Hz), 3.505 (dd, 1H, J=3.6 Hz, J=10.6 Hz), 3.3 (S, 3H), 1.268 (D, 3H, J=6.4 Hz).

Workup

temperatureAfter cooling to room temperature the suspension
extractionextracted with methyl-tert.-butyl ether
washThe combined organic phases are washed with brine
dry with materialdried over MgSO4
customThe solvent is removed in vacuo

Sources & evidence

ORD record: ord-f0c070065e7c42a7b8dbfe1016517ccf
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420642B2

Reaction notes

Loading…