Chloroacetaldehyde → (3-Cyclopentylmethoxy-5-phenoxy-pyridine-2-yl)-thiazole-2-yl-amine

HRID 1966245Notes

Reaction equation

[CH:1]1([CH2:6][O:7][C:8]2[C:9]([NH:21][C:22]([NH2:24])=[S:23])=[N:10][CH:11]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:26][CH:27]=O>CN(C=O)C>[CH:1]1([CH2:6][O:7][C:8]2[C:9]([NH:21][C:22]3[S:23][CH:26]=[CH:27][N:24]=3)=[N:10][CH:11]=[C:12]([O:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 100 °C

Procedure

(3-Cyclopentylmethoxy-5-phenoxy-pyridine-2-yl)-thiourea (0.68 mmol) is dissolved in DMF (3 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-Cyclopentylmethoxy-5-phenoxy-pyridine-2-yl)-thiazole-2-yl-amine (“A29”) is obtained after reversed phase column chromatography (acetonitrile/water+0.1% TFA) as yellow solid in a yield of 43%. HPLC (method C): 2.03 min; LC-MS (method A): 2.22 min, 368.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 7.705 (d, 1H, J=2.1 Hz), 7.509 (d, 1H, J=3.9 Hz), 7.387 (t, 2H, J=7.9 Hz), 7.32 (d, 1H, J=2.1 Hz), 7.143-7.119 (m, 2H), 7.029 (d, 2H, J=7.9 Hz), 3.992 (d, 2H, J=7.1 Hz), 3.787 (br, 1H), 2A49-2.389 (m, 1H), 1.853-1.829 (m, 2H), 1.619-1.547 (m, 4H), 1.371-1.320 (m, 2H).

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-e7fa7ec5318a49f38f7d9523fde44140
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420642B2

Reaction notes

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