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

HRID 1966252Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH2:4][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:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:11]=1.Cl[CH2:24][CH:25]=O>CN(C=O)C>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([NH:19][C:20]2[S:21][CH:24]=[CH:25][N:22]=2)=[N:8][CH:9]=[C:10]([O:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:11]=1

Participants

Conditions

Temperature: 120 °C

Procedure

[3-(2-Methoxy-ethoxy)-5-(pyridine-3-yloxy)-pyridine-2-yl]-thiourea (0.34 mmol) is dissolved in DMF (1.2 ml) and chloro-acetaldehyde (1.0 eq., 55% in water) is added and stirred 90 minutes at 120° 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-ethoxy)-5-(pyridine-3-yloxy)pyridine-2-yl]-thiazole-2-yl-amine (“A31”) is obtained after reversed phase column chromatography (acetonitrile/water+0.1% TFA) as yellow solid in a yield of 37%. HPLC (method C): 1.17 min; LC-MS (method A): 1.07 min, 345.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 10.403 (s, 1H), 8.477 (d, 1H, J=2.7 Hz), 8.398 (dd, 1H, J=1.3 Hz, J=4.6 Hz), 7.832 (d, 1H, J=2.3 Hz), 7.558-7.533 (m, 1H), 7.500-7.475 (m, 2H), 7.456 (d, 1H, J=2.3 Hz), 7.116 (d, 1H, J=3.7 Hz), 4.279 (t, 2H, J=4.6 Hz), 3.771 (t, 2H, J=4.6 Hz), 3.339 (s, 3H).

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-80ce9aa61a0748ce8cdcd2d6a79e9f27
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420642B2

Reaction notes

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